Welcome. Just so you know, the faculty is just as nervous as you are, but for different reasons. We sit in the back and discuss these questions as they go back and forth. We disagreed on some of the receptor questions and whatnot, so when I get to it, I'll talk to you. So full disclosure, this lecture on the original one hour times two, Janice Zimmerman is an adult ER attending who gave it and speaks very quickly. I'm a native New Yorker. We have mandibular tachycardia, I can speak even quicker, and I think that's why they gave these to me, because I have to end up the day with neuro. So not only are we teaching you for an exam, but I feel strongly we should give you something else. So I will be irreverent. The surgeons really are going to take it on the chin throughout the afternoon. So when you go back and you're arguing with them, one of the things I always say is, what is an intensivist? So an optimist sees the glass as half full, the pessimist sees the glass as half empty. The intensivist keeps the surgeon from knocking over the glass. So with that, we'll get going. Okay. All right, so I have no disclosures. I've got three kids, a grandkid, I'm broke. So when you're talking about toxicology, there's a gazillion drugs out there, what's the best way to put this together? So what I did, I looked at the most recent annual report that you can look at online from the toxicology centers. And I thought, and the way I broke it up, so you've got three columns here. All exposures, these are the top 10. So analgesics, household cleaning products, cosmetics, antidepressants, I'm not going to read this to you. I can save time like everybody and just say, memorize this chart, and I'll go on. I've been trying to count how many charts you've been told to memorize, and I've lost count. But basically, these are the top 10 things. And so then let's say, I've got to decide what am I going to teach people, what should we learn? So let's look at the fatal exposures. Let's focus in there. So sedative, hypnotic, and antipsychotics, opioids, alcohol, street drugs, acetaminophen. So we'll go through examples of each of these 10. And then lastly, the fatal exposures. So there used to be quotes years ago, and they said, one pill can kill, and things of that sort. Any pill can kill. It's related on dose, toxicity, and whatever. So we're not going to spend a lot of time on that, and that's sort of, I like mythbusters, and we'll really, again, the surgeons are going to take it, in particular the neurosurgeons, when we get to that. But so the fatal exposures, and one of the things we see is polypharmacy, right? When you look at your ingestions, in particular with the kids and the teenagers, they're just going up. So we're going to do toxidromes next, and we'll walk through each of them, but a lot of times, one drug offsets the other. So it may not be as clear-cut a toxidrome, and I'll come back to that. But what makes kids unique? What do we worry about differently than my adult counterpart, who used to give this lecture? So there's developmental changes in drug disposition. So you're going to hear a talk from a real pharmacist, not me, in a little bit, so I'm not going to talk a lot about it, but ADMA, absorption, distribution, metabolism, excretion, is different in younger kids. Dermal absorption can be, they have a higher surface area. Airborne toxins, they've got higher minute ventilation, they breathe quicker, they're lower to the ground. Higher metabolic rate and decreased reserve. Dependence on the diaphragm and abdominal breathing, so we'll talk about fatigue and respiratory failure, not even drug-related, not only drug-related, but also when we get into the neurologic disorders. They have a lack of glycogen stores, they've got tiny little livers, they don't have big supplies like we do. Limited cardiovascular reserve. They can't increase stroke volume. So to keep cardiac output, cardiac output, heart rate times stroke volume. So they're a little more tachycardic. Neurotransmitters are different. Ion channels, there's a lot of things that go on developmentally, and we'll talk a little bit in depth in the second talk about the autonomic nervous system. And then lastly, the opioid receptor agonist, isomers, and kids are just more sensitive. So again, memorize this chart. So this is just an approach to an unknown ingestion, and we all know the airway breathing circulation. So one of the handful, when you get which of the following would you do, and there's like five in a row, five in a row, four in a row, start with the least toxic. Remember, do no harm. So when the choices are there, and like ECMO might not be the first choice, right? So just think it through, and we'll go through that when we do the cases at the end of the day. So we talk about a toxicologic physical exam, because we're looking for hints. It's the same way when you read the STEM, which trust me, on the real exam are nowhere this long. Time management is another key concept. So you look at the number of questions. I think the sub boards are 200. They tell you how much time you have. Do the math. You probably have a little bit over a minute per question, and they're all worth the same. So as you're going through the test, just think about that. But so vital signs, we'll talk about that in particular with the toxidromes. Pupillary diameter. Nowadays, a lot of you may have the pupillometer. You can actually measure it rather than, come here, what do you think? Is that three? Is that four? The nurse is smacking you. No, no, it's this, and you're going back and forth. Nystagmus is a finding associated with certain entities. We'll talk about them. The mucous membranes. Are they wet? Are they dry? Skin. Moisture. Is the sweat glands working? Because everything's got an asterisk with it, so we do the autonomic nervous system. The innervation to the sweat glands get an asterisk. We'll come back. Mental status. Muscle tone. You know, a floppy, you know, good muscle tone. Reflexes. Absent. Present. Clonus. Bowel signs in the bladder. So what are we really worried about? You know, the one thing is we have the ED as a good buffer. You know, there's always all the jokes between the ICU and the ED. They're dealing with this first, so they're kind of going through a lot of what makes our lives a little bit easier at times, perhaps not all the time. But so what's life-threatening? What are we really worried about? With this unknown ingestion, the kid comes in, we suspect that it's ingestion. We've got to rule out the differential. What else could it be? But seizures and status epilepticus, which we'll talk about later, altered mental status and coma. Not an unusual presentation for many different types of ingestions for kids. Respiratory. We can see respiratory failure, just muscles are involved, or it can be central effect that they're hypoventilating. Neuromuscular weakness. There are drugs that can cause direct pulmonary toxicity or the patient aspirated while we were fumbling through the diagnosis and trying different things, or pulmonary edema. Okay. So again, everybody loves to say, memorize these charts. So it's funny when you're young, you love mnemonics to make things easier. As you get older and you know like 200 different mnemonics, and each one's got seven parts, you're like going around, it's like, Jesus, I got the four, getting a five, and then you look and you say, you know, I could tell you the last two, but it'd be better if you looked them up. And then you just, that's a teaching point. But anyway, the etiologies of coma. If you can remember your vowels, which most of us can do, A-E-I-O-U, and then add the word thips with a little bit of a lisp at the end, and you just sort of run through this, and this gives you 98% of the causes of coma. And again, we're going to focus here in particular on ingestions. So besides the pulmonary status that can be critical and the neurologic, cardiovascular, the one that scares many of us, scares me to death when they come in, so drug-induced tachycardia, malignant dysrhythmias, so we'll talk about those, like sympathomimetics, anticholinergic. There's certain drugs when you see tachycardia you should just think of as a possible ingestion. And then even more scary is the drug-induced bradycardia, and we'll go through the drugs that do that and what we do for it. And then not to forget hypothermia, because Supta, when she gave her talk this morning, she showed you that chart to memorize, and the different things. So we'll walk through those, but it's hypothermia is something in the background we don't want to forget because it increases metabolic demand. So ultimately it could cause issues in the CNS that may not have been there early on if we focused on it. So we always send off labs. So what labs are useful and what labs aren't? So the exam isn't a math test, but there are just some basic calculations you have to do. So anion gap. So on my left, the non-lactate is sort of the elevated anion gap, and then we've got the lactate on the right side. So again, each drug is different and you're going to have different findings. But when we send off these labs in general, this is why electrolytes become real simple. We can do the basic calculation for the anion gap. And then urine toxicology. The one thing I want you to take away from it is, in particular with the opiates, we've seen a massive increase in opiates and fentanyl in New York. Fentanyl does not show up on the basic urine test, and we'll go through that later on when we do toxidromes. But again, we always send off the urine toxicology. It's not going to come back right away, and we've got to manage the patient based on their signs and symptoms. So what else did I always say? Well, let's get an EKG. So let's think about when can an EKG be helpful. So on my right is the QRS widening agents. So we're worried about, because that can go from a tachycardia to a malignant, some sort of ventricular dysrhythmia there. And then we also worry about QTC prolongation. So again, just here, kind of listed the drugs that can cause that, just so you have an idea. And again, when we do the toxidromes and the samples, I think we can make this a little easier to go through. And this is just a point I want to mention. I put it in here so I don't forget. So sodium bicarb as an antidote becomes very helpful, in particular, in certain ingestions, and it's usually the antihistamines, antipsychotics. So we talk about anticholinergic poisoning. One of the things is as the QRS gets wider, it's a predictor if they're going to cease and if bad things are going to happen. So we'll come back to it. But as you're studying, I put this in here for another reason, you think about what we're going to do for these patients and to change the protein binding of the drug, we're playing with the pH. Always think of the side effects of what you're going to do, and then come back to risk management. Never mind for taking a test, but for managing patients in general. And then we always send levels on everything, but there's only certain drugs that you really need a level on. There are only a certain amount of antidotes that are available to us. One caveat, most antidotes have a shorter half-life than whatever the offending toxin is. So you've got to keep that in mind, too. And so I just put this sort of in here for what would be helpful, the drugs that we may have to do something a little bit more extreme for. Eighty-five percent of ingestions do fine, don't even get admitted to a hospital. Five or ten percent come in and get usually observed for 24 hours. And then it's the small, the four or five percent that come to intensive care. Really basic management, and aim for normal vital signs in almost any disease state, a patient will do fine. I'm not going to talk about enhanced elimination, because we have a pharmacist here that knows far more about it than I do. But there are certain drugs that we can hemodialyze. The MDA charcoal, we've gotten away, because if you don't give charcoal in the first hour, it doesn't work, except there's always an asterisk for a handful of drugs. And what you're doing by giving multidose activated charcoal is you're using the gut as a sink. Everything gets absorbed, concentrated in the gallbladder, gets squirted out, and then goes around. So you're playing with the enteropathic circulation with charcoal. But again, aspiration of charcoal is not benign and rare, but not unusual. So we have to be careful with that as well. And then urinary alkalization, we'll talk about that a little bit later when we do the favorite toxins that they like to test you on. Salicylates is always way up there. So I'm just going to do a couple of the favorite ones, and then once we've had enough or we're close to the end wave, I have a little bit extra time later on so I can balance all this. So anyway, we'll start with acetaminophen, right? We heard this morning, leading cause of liver failure, liver transplant, and things of that sort. So we know there are four stages of it. But again, we want to prevent. So we've seen chronic ingestions or acute on chronic. So the mucamyst that we give, we'll come back to it in a second, how it works, can be given, it usually says eight hours. Favorite question is you get a kid that comes in like 18 hours later, so you're going to give the mucamyst for up to 24 hours. So I'm just picking on fun facts with these because there are just too many toxins to go through. So the acetaminophen, I don't know, does this work? So basically what happens is Tylenol gets in the body, gets metabolized, and it comes down the enzyme pathway and it gets made into a toxic NAPQI metabolite. Now usually with standard, we take it, we take our Tylenol, it gets metabolized, we pee it out, not a big deal. What happens when you get the massive overdose and enzymes get saturated, they can't handle it and do the glucothione conjugation. So what you're giving is glucothione substitutes when we give the mucamyst or the antidote. So you're providing help to the enzyme system. So a lot of times when you get into trouble, it's because the transmitter isn't being made, can't get to where it needs to go, or something's happening on the receiving end. So this is kind of an example of that. So it's the toxic metabolite, the NAPQI, that causes the problem. And we get through by giving them, you know, you look at the level, you can look under that. They're not going to test us on, you know, we keep saying, what are they going to ask? They are us. Because there's many people sitting in this room who I have left that have sat on the board and whatnot. And we're always told, I've never sat on a board, full disclosure, but I unpick you, I've done a lot of question writing, you're always told this should be easy, you should open a textbook, be able to find the answer. Blood is shed at night when we go over these questions. And then we try and guess who wrote that one. But anyway, sulfonylureas, right? The problem we see now with longer acting drugs, it's great if you're the person that's taking them. But when the younger kids get a hold of their grandma or grandpa's sulfonylurea, they can get into trouble. And what's the trouble they're going to get into? They're going to get hypoglycemic. Of all the insults to the brain, hypoglycemia probably portends for the worst outcome. It's the least forgiving. So again, the mnemonics are here, hobbies, so you can think about for sulfonylureas. And on the other side, I have the side effects if you're hypoglycemic, or it's a beta blocker ingestion, you're not going to see the neurologic findings. So there can be some subtleties. And when we talk about the toxidromes, we'll go through what those can be. And I bring this back to the toxicologic physical exam. We really have to be able to do a really fine neurologic exam in a pediatric patient. And we'll talk about that later this afternoon. But again, I put these charts in here for you to be familiar with. I'm not going to say memorize. Another common or easy to write questions for is methemoglobinemia. The general piece they give it to you is somebody who's drinking well water, or mom or dad made up some green leafy vegetables, stuck it in the fridge for a couple of days, and the kid gets oil. They've got some sort of GI infection with the nitrite-producing bacteria. So one of the questions, and I heard one of the presenters talked about, we talk about the chocolate brown blood. They were trying to ascertain if the central line was in the correct place. So that's a picture of what methemoglobinemia, what the blood would look like. Once the level gets about 15 or so, that's when you'll start to see the change. And the reason I put the pulse oximeter here, because we're going to talk about carbon monoxide in a bit, but you can see that the peripheral pulse oximeter can't tell the difference between the, I'm trying to look here, the methemoglobin is the red. So when they intersect, it can't tell the difference between them. It's the same thing with carbon monoxide poisoning. It can't tell the difference between oxyhemoglobin, deoxyhemoglobin. So in methemoglobin, the default goes to 85%. So if you get a kid that's got teething pain, and the parents are given some of these oral over-the-counter pain meds, you can see methemoglobinemia. And the other way is how do we treat it, methylene blue. So the way to think about it is, if you go through this entire concept on the bottom, but the bad hemoglobinemia is ferric, R-I-C, so it's 3+, us, 2+, is the good iron that works with hemoglobin. So the main goal when we give the methylene blue is to get from the ferric, the R-I-C, the 3+, back to the 2+, that can work with the hemoglobin. Calcium channel blockers. These are really bad, and we have long acting. So again, I'm not going to read exactly how we work through all of these. We'll see it later on some questions. But basically, we treat them with fluid resuscitation, and a lot of times you can get by, start with just IV supplemental calcium. Calcium chloride is directly active, doesn't need first pass through the liver. Some of us are more comfortable with calcium gluconate. And then there are more extensive therapies that are out there, not always approved. But when you get into these life-threatening ingestions, always should be on the phone with your poison control center to get some advice with what to do. So if you get down to the bottom, when things are getting bad, they talk about other things that we can do. So we've given the calcium, and the kid's still not doing well. The hyperinsulamic euglycemic therapy that's out there, we use it for this and for beta blockers. And basically, what it is, is the calcium channel blockers and beta blocker can cause cardiogenic shock. So instead of doing this, you're starting to get this. So the stunned myocytes alter their metabolism from free fatty acid to carbohydrate metabolism. So to help offset that, it causes insulin resistance. So to meet the cardiac demands, improve inotropy, get rid of the vasodilatation and the hypotension, improve organ, we can give this combined, and you mix them together. You don't give an insulin bolus. You start them with insulin that's mixed in the bag together with the D25, D50. Again, you can look up the dosing on the site. If you notice, rarely do we give dosages on test questions. The problem is, because things change so quickly, it's like every textbook, the first paragraph is always a disclaimer about pharmacology. The second drug to think about for this is glucagon, again, both in calcium channel blockers and beta blockers. So you're talking about the cardiovascular system. You're talking about alpha and beta receptors. And Raj in the cardiac had a great chart there listing what all the receptors are, where they are, and what they do. It's worth taking a little bit of time and looking. If I had to pick 10 top charts I would look at, that would be one of them. But it's an antidote for both. And what it does, it circumvents the poisoning for the beta 1 receptor, basically increases cyclic AMP. So it gives the heart more oomph for its money. So glucagon is fairly benign. It increases both the onotropy and the chronotropy. And then lastly, this is not recommended, this is only approved basically for bubuvacaine toxicity, for local anesthetic toxicity. However, it's been used more frequently, and there's case reports, and everybody reports their successes, the failures we don't read about. But sometimes when nothing else is working, we may consider using a lipid emulsion. And so the thought is that it works as a lipid sink, because you're giving this amount of lipid that's circulating, that the drugs will just redistribute into the fat. And you're sort of taking it out of play, taking it out of the circulation. It helps provide supply for free fatty acids. Remember, they switch to carbohydrates, so you're giving them substrates, you're going to help the myocardium. You've probably already done your glucagon, so you've done the most you could for that, things of that sort. There are multiple complications with it, renal failure, cardiac arrest. And again, it's not recommended, but when you go through the algorithms for beta blocker ingestions and for calcium channel, you'll see when you get down there. So I just want you to have heard about them and feel comfortable, because you may get asked, and you'll see a sample this afternoon, which of the following would you do first type thing? Carbon monoxide, how are we doing for time? Two minutes? Yeah, but since you have the other talk, you're done. Okay. Oh, I'll be back. Okay. That's why they brought me from New York, because I could really do this as quick as I can. Anyway, actually, watch Janice's first, because she is super fast. She was pretty quick too, but basically, carbon monoxide, it's sort of an odorless, colorless gas. And the stem usually helps you out with it, because it's like an entire family comes in with flu-like illness, right? Small pets have died, because pets breathe quickly. So the rats, the cats, the dolls, and you've got this history of a family is sick, looks like flu, little three-year-olds crying because the hamster died, things of that sort. So you want to think about it. The stem is usually helpful. However, there's different symptoms at different levels, right? Smokers walk around with a level of two or three, slight headache. So the whole question comes up, and again, I put this back in there again, because the peripheral pulse ox is going to be reading 98, because it can't tell the difference. You need a carboxyhemoglobin level. There are newer pulse oxes out there. They're very expensive. Who can tell the difference? Where I am, I have a hyperbaric chamber, so I can go down and beg to borrow the good pulse ox to figure this out while you're waiting for the labs to come back. But so hyperbaric therapy, the reason I mentioned hyperbaric therapy is yesterday, again, the cardiac talk, we heard about the O2 content equation. They always say ignore the 0.003, because he said it yesterday. However, the way hyperbaric oxygen works, we increase you to three atmospheres of pressure. So if you think back on how to calculate the AA gradient, we put in the barometric pressure minus 47. Well, this is three times that. So basically what happens, you're massively increasing that dissolved oxygen, and you're getting up there, right? Because normal lungs and heart give me 100% oxygen, and we'll come back to how you treat before you get them into the hyperbaric. But now you've got 100% at three atmospheres. You put enough dissolved oxygen in the blood, so the AvdO2 there, you could have saline just flowing through them with the hyperbaric, because it provides what they need until the carbon monoxide goes away. So the half-life of CO, I think I put it on. So this is just the pathophysiology of how the bad things happen. But so what happens is in the hyperbaric, at the fire scene, the firemen always put them on 100%. Half-life of carbon monoxide untreated is about four to six hours. 100% breaks it down to 90 minutes. You put them in the hyperbaric chamber, you get it down to about 25 to 30 minutes. It's not benign to dive somebody. Most institutions, and it's very controversial, will use a level of 25 to dive you. Like I said, everything's got an asterisk. If you've got a pregnant mom, we dive them at 15 because the fetus has the left shift of the hemoglobin curve because of fetal hemoglobin. So to give the benefit of the doubt, we dive them at lower levels. If there's any loss of consciousness, any neurological cardiac finding, we'll send them down in the hyperbaric. Not any controversial to do a re-dive and to take them back. The data's all over the place. But again, it's not an uncommon toxin. Salicylates for the sake of this, sort of a general PEDS thing, so I'm going to speed up a little bit. I've given you these charts, and it basically tells you what doses and when you're going to get into trouble. It's always helpful to guesstimate, but again, doing pediatrics is like veterinary medicine. We don't have all the information we would like to make a decision. Iron, again, is another one because it's toxic. It goes into syndromes. It binds to the GI epithelial cells, causes leaks, causes all kinds of problems. So iron is another, I think, fair one that I would take a look at this. And then, I apologize, this should have been moved up, the beta blockers. So this is a really bad one, just like the calcium channel blockers. So we've got beta receptors on the heart, the kidney, and the fat tissue. Beta-1 agonists produce inotropy and chronotropic effects and renin release. Beta-1 selective antagonists, so atenolol, metopropolol, esmolol. Then you've got beta-2 receptors. So this is where the receptors get really important, what you have where, and what we look for. But the beta blocker toxicity results in bradycardia and hypotension. So again, if they're asymptomatic, we can treat the hypotension with some fluids. But then we have to think about what are we going to do next. So again, we're going to go back to sort of the glucagon. And then we would go to the insulin glucose regimen. And again, there are case reports out there of using the lipid. Using glycol, because they're going to want you to know how to calculate an osmolar gap. So we all know how to do osmolarity, 2 times the sodium plus the BUN divided by 2.8, glucose by 18. You get your number. The lab can do a measured osm, and they'll call you and say, the measured osm is 340. And you're doing a calculated, it's like 290. So they have this massive osmolar gap. So there are very few things that cause that. One of the major top three are different alcohols. So methanol, ethylene glycol, those are the problems. And the reason I mention it is because the formipazole blocks the enzyme, and actually we have an antidote that can work. Sometimes you'll see pictures of oxalate crystals. How many in the room have ever seen an oxalate crystal? No, Jeremy, you don't count when we ask these questions. You and I are the only two to put PD catheters in, too. And all the young'uns are like, what's a swan? My guys think it's a bird. Anyway, we'll talk more about this with the toxidromes when we come back. But you want to be able to figure out the osmolar gap, what's causing it. In the old days when we used lorazepam infusions, lorazepam itself can cause problems. And you pick it up with an acidosis, but you find an osmolar gap because it's the alcohol that's causing it the problem. You tell me it's time. We're done. Treatment of severe hypothermia should be a priority. Hypotension, secondary poisoning, for the most part can be treated with fluids, but if you need medications, benzos and norepinephrine, we'll come back to that in the next talk. And urine screens are fraught with error. And wherever you are, memorize your poison control number. You should always get them involved.

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