Okay, I'm not going to repeat the title, I'm not sure who came up with that, but basically I'm going to focus on the diagnosis of the most common cardiotoxins that are involved in overdose using primarily clinical presentation, and then talk just a little bit about the immediate treatment, and then the more advanced treatment will be covered by the next speakers. I have no conflicts of interest, and I will try to point out some drugs that I have listed that are off-label uses, that happens a lot in toxicology. So when you approach a patient with a potentially cardiotoxic overdose, you're going to follow kind of some steps. You're going to ask for history, you're going to ask what they took, how much they took, when they took it, but often that information is not available, or it may not be accurate. So you're going to really rely on two things in the physical exam, the vital signs, particularly the heart rate and blood pressure when we're talking about hearts, and you need the neurologic exam because those findings will kind of help you put together that clinical syndrome or toxidrome that will help you identify, hopefully, a category of drugs, and then, of course, when we're talking about cardiotoxins, you need the electrocardiogram to assess some of the toxic effects. I will say you don't need to worry about urine toxicology or other toxicology tests because you're not going to have the results, and they're really not that helpful in managing your patient. Again, the steps in managing an overdose are the same for a cardiotoxin as others. You're going to start with the ABCs, and here for hypotension with a cardiotoxin, you still start with fluids as the first intervention. These patients need to be hooked up to a monitor, obviously. If they present within one to two hours of ingesting a drug, you may consider the use of charcoal to absorb the drug in the GI tract. The labs that are going to be helpful with cardiotoxin are a troponin to assess for any myocardial injury, and then, of course, you want to know your electrolytes, particularly potassium and magnesium from your basic metabolic panel. You may, at the very last step, which could happen at the very beginning of your evaluation of a patient, may have an antidote, or more likely, and the drugs we're going to be talking about, specific interventions that you can consider. When we think about cardiotoxins, their toxicity is usually going to have mainly effects on two things, altering the cardiac conduction or myocardial function. Conductive abnormalities are going to usually be slow rhythms or fast rhythms, and then the altered myocardial function usually presents as hypotension, and this could be due to the negative inotropic effects of a specific drug or potentially vasodilatation, which we'll talk about with some of these overdoses. These effects on the heart are then combined with other clinical manifestations, and they will usually give a kind of a typical presentation of some of these cardiotoxic overdoses, so a very common one is bradycardia and hypotension. We also see a lot of patients present with tachycardias, and that's usually associated with either a sympathomimetic toxidrome or clinical syndrome or an anticholinergic toxidrome, which we'll talk a little bit more about. Some patients may not have very obvious other clinical manifestations, but they may have an abnormal EKG, so we'll also talk about that group of patients. And then, of course, the worst patients are those that present in cardiac arrest or develop cardiac arrest while you're caring for them. Thankfully, that's a small number of patients. So let's start with bradycardias. This is a list of drugs that can be associated with bradycardia in overdose. The ones that we really want to focus on are beta blockers and calcium channel blockers because this is really the most common cardiovascular drugs that are implicated in overdose. We just don't see clonidine and digoxin overdoses as much because those drugs are not being prescribed to the patients. So the clinical manifestations of these overdoses are due to the negative inotropic and chronotropic effects of these drugs. So you get the bradycardia and the hypotension. Now with hypotension, that's usually due to the myocardial depression, which occurs with both classes of drugs. But you can also see a contribution from vasodilatation, and this is due primarily to the dihydropyridine calcium channel blockers, such as nifedipine and amlodipine. Altered mental status is a clue to beta blocker overdoses because there are more of the beta blockers that actually cross the blood-brain barrier. So that may be a clue if you don't know which class of drugs you're dealing with. The hallmark for calcium channel blockers is the presence of hyperglycemia, and you'll hear more about how to manage these overdoses in the next presentation. But it turns out that they also block the calcium channels that inhibit release of insulin from the pancreas. So that's a hallmark. Now, some have said you can see hypoglycemia with beta blockers, but that's not a consistent or reliable finding in those overdoses. So thankfully, within these classes of beta blockers and calcium channel blockers, there's only a few drugs that are really associated with severe cardiotoxicity. For the beta blockers, that's propranolol, and that's probably due to its high permeability across the blood-brain barrier, but also due to the fact that this is one beta blocker that can prolong the QRS interval. Of the calcium channel blockers, it's the non-dihydropyridines, diltiazem and verapamil, that are most frequently associated with severe cardiotoxicity. All of the drugs on this list are available in sustained-release forms, and that's how they're usually prescribed. That's important because you have to recognize you may have delayed toxicity while it's being absorbed, and you also may have prolonged toxicity with those sustained-release forms of medication. Let's look at the EKG findings, and obviously, in bradycardia, the most common finding is a first-degree AV block that you can hopefully see on this EKG, and the good thing is it's very uncommon to see third-degree AV blocks with these. You should look for that widening of the QRS because that is another potential indicator of propranolol overdose rather than a different agent. When approaching the management of these drugs, beta blockers and calcium channel blocker overdoses, I'm just going to emphasize some of the immediate actions. Everybody gets atropine, and it just doesn't work, so if you don't want to give it, that's fine, but everybody gets it because there's a slow rhythm, and it's something you can get very quickly. With beta blockers, it's been said that glucagon is kind of the antidote, and this is due to the fact that glucagon acts as a positive inotropic agent. The dose is not standardized, but usually you'll see recommendations of 3 to 5 milligrams as a bolus, and then if you have positive effects, you start an infusion at 2 to 5 milligrams per hour. Calcium is the antidote, if you will, if you know you're dealing with a calcium channel blocker, and that's 1 to 2 grams of calcium chloride. You can go higher than that. If you have a positive effect, then you need to start an infusion. Just remember, if you're using calcium gluconate, you have to give three times as much to get the same amount of elemental calcium into your patient. When it comes to hypotension and vasopressors, you need to remember that there is no one specific vasopressor that is recommended or proven to be effective in these types of overdoses. The response of an individual patient is unpredictable, and you may need to use very high doses, but what you need to look at is, what is the problem? Am I dealing with vasodilatation from nifedipine, or am I looking at negative inotropic effects from propranolol? So norepinephrine is still the first pressor that's usually recommended, but epinephrine may be an option when you're looking for more beta 1 effects. Remember, unfortunately in the heart, those beta receptors are blocked if they've overdosed on a beta blocker. So the other things we'll leave for the other speakers to cover and move on to tachycardia. So tachycardia in an overdose is usually associated most commonly with sympathomimetic or anticholinergic drugs, and also I have to add caffeine on this list as well now. So for sympathomimetic drugs, as you can see, this is cocaine, amphetamine, it's a list of really illicit drugs that individuals choose to use recreationally. And then the anticholinergic drugs, and this incorporates a lot of medication, so it's all the antidepressants, all of them, even SSRIs. It includes your antipsychotics and neuroleptics, even the ones we use in the ICU, such as haloperidol, catiopine, and antihistamines. Caffeine has different types of effects. It blocks adenosine receptors rather than having a release of neurotransmitters. But poisonings with caffeine are being seen due to ingestion of tablets, pills with caffeine used to stay awake, and also with ingestion of the energy drink. So just be careful how many you're drinking today, or we'll have another arrest possibly. These again have a similar presentation clinically, these toxiderms, they all, both sympathomimetic and anticholinergic drugs can have tachycardia, hypertension, tachypnea, and often an increase, not a really high increase, but a slight increase in temperature. And they have the agitation, the psychosis, they have dilated pupils, and they may be associated with seizures. Now when you're trying to distinguish between an anticholinergic type of drug or a sympathomimetic, there are some potential clues you can use, although the approach to management is not that different. So with sympathomimetic drug overdoses, you're going to see them be diaphoretic, bowel sounds are increased. A lot of times nobody listens to the bowel sounds in an overdose patient, but you might consider doing that. With the anticholinergics, these are the dry as a bone patients, so they have dry skin, dry mucous membranes, and their bowel sounds are decreased. They also may have urinary retention, but that's not something that you're going to probably pick up on right away when evaluating these patients. The EKG findings, of course, typical as this one illustrates is a wide complex tachycardia. It's sinus tachycardia is most common, and then that increase in the QRS and the increase in the QTC are evidence of that conduction abnormalities that you see with these drugs. Now the threshold for the prolongation of the QTC is chosen as greater than 500. Now for most people, the normal is less than 440. As you know, it varies with age, gender, and the heart rate. But the greater than 500 has been associated most commonly with an increase in mortality and also the presence of lethal arrhythmias such as torsades. So that's why you want to look for that greater than 500 milliseconds on that QTC. The other pattern to look for is a brugada pattern, which is illustrated on this one. You look for that kind of camel hump in V1 to V3. This has been seen particularly with cyclic antidepressants, but also with a lot of other antidepressants and cocaine as well. So look for that. VTAC and VFIB you're going to pick up on. That's the ones we really don't want to see. We want to prevent those, if at all possible. Now I also want to mention those patients who have that abnormal EKG, but they don't necessarily have tachycardia. And this actually is probably the majority of patients that you're often worried about and that you want to do something with. And these are the patients that have similar EKG findings that increase in the QTC, the QRS, or brugada pattern, but their heart rate may be normal. They may even be bradycardic. So the drugs that can do this are similar. So the antidepressants, the antipsychotics, and neuroleptics, and the antihistamines. But I want to also call out that we have to put some opioids on this list, methadone, and loperamide. We could also add azithromycin. We could add fluconazole, but again, we don't see too many cardiotoxic effects when we use these clinically. But I do want to mention loperamide because we're seeing more overdoses with this. As you know, it's an over-the-counter medication. The reason it doesn't usually cause CNS depression is because it doesn't cross the blood-brain barrier well. But what happens, this has now been called the poor man's methadone. So in this opioid epidemic, if someone cannot get their preferred opioid, they will go and buy a lot of loperamide and take it. And it's associated not necessarily with tachycardias or anything, but normal or decreased heart rate. But the dysrhythmias that are described are wide complex tachycardias and particularly torsade. And these patients typically present with either cardiac arrest or syncope. So keep this in mind. Also giving naloxone to these patients will not reverse these cardiac effects. The same would be true for methadone. You have to treat the cardiac toxicity. So let's talk first about managing unstable tachycardias if you have that type of patient or the cardiac arrest. And it's recommended that you follow ACLS protocol, including the defibrillation recommendations. And then sodium bicarb is the next step if the patient is unstable or has an arrest. One of the things you have to be careful about is using an antiarrhythmic that prolongs the QTC because that's often the damage done by the cardiotoxin. And of course, amiodarone prolongs the QTC. But having said that, I will tell you that there are many experiences that have been described where amiodarone was used to treat some of these arrhythmias. And then advanced interventions will be covered by another speaker. So the other unstable tachycardias that you might see would be torsade. I think obviously you'll give magnesium in this setting. Various reports have described use of amiodarone and lidocaine in this setting and also attempts to overdrive pace when you have torsade due to a cardiotoxin. So I just want to finish up my last slide with talking about that group of patients that is probably the most in number that you see is the patient who has an abnormal EKG but doesn't necessarily have a significant tachycardia. And the question is, what do I do? So when you see that widened QRS, the prolonged QTC, you have to do a risk assessment. Because the risk of a dysrhythmia varies tremendously depending on the drug. As an example, bupropion, it will increase the QTC even with therapeutic doses and overdose. But it is very rarely associated with significant dysrhythmia. So in that case, you may not need to do anything. But it's also been recommended not to use just the corrected QTC because the formula that's used, BESSETS, usually tends to overcorrect. So some have suggested not only looking at the corrected QTC but look at the uncorrected. And if the uncorrected is prolonged and your QTC is prolonged, then you probably have a greater risk of deterioration in that patient. So obviously you're going to monitor these patients. You're going to repeat the EKGs, looking for resolution of the abnormalities. You're going to look at your electrolytes, correct those electrolytes. And then the question is, should I give my patient bicarb? And I think this is, again, where your risk assessment comes into play. Not every patient with a prolonged QTC or increase in their QRS needs bicarb. So if the patient has significant other complications due to their overdose, then that's a higher risk patient. So if they have altered mental status, they have hypotension, then that patient should be treated with bicarb. So I'll stop there and go on to the next speakers. Thank you.

cardiotoxic overdoses

diagnosis

management

beta blockers

calcium channel blockers