for that is my contacts did not agree with me this morning, and my glass prescription is a few years older as well, so certainly bear with me here and we'll certainly get through this. Great, as I said, my name's Brad Hogan. I'm from the University of Rochester, and the medical center is about a 900 to 1,000 bed patient. We are a level one trauma center as well, and we also have the luxury of having a toxicology team available to us, as well as an addiction medicine team in addition to that. So, I have no actual potential conflicts of interest or disclosures in relation to the program and presentation, and our objectives through this are going to be to offer guidance and to recognize patients with the most common toxidromes, and to understand who may require intensive care unit admission. Oftentimes, that is pretty black and white and concrete, who we need to admit to the ICU. Other times, that is not. And keeping in mind that the 30 minutes approximately that I have for this presentation, there is a vast amount of information in the toxicology world that hopefully will cover a lot of it and give you some foundational and conceptual ideas, but we are not gonna be able to touch upon all of it. In addition, we'll summarize some up-to-date evidence on how to stabilize, treat, and prevent complications of various toxidromes of patients admitted to the intensive care unit. First, we're gonna take a look at some of the prevalence of overdoses, just to give you an idea of where we are in the United States. Just by a show of hands, who has taken care of a patient that has had an overdose or some type of withdrawal syndrome? I would say that's about 95 to 98% in the room with this. So this spans across all of our interdisciplinary ICUs as well as hospitals or general surge floors and medicine floors as well. It's certainly known that the U.S. is struggling with a drug overdose epidemic. Accidental and intentional poisonings from both illicit and illicit substances remain a major cause of morbidity and mortality worldwide. By taking a look at this graph, we can certainly see on our x-axis that roughly over the last eight years and going up in the number of deaths on the left in 20,000, just looking at the trajectory of the graph, we are certainly heading in the wrong direction. And this was based off October of 2023. Of course, in January 2024, some recent data and as of December, this continues to increase. This next graph that you have on the right as well does also show an increase. This is going back to 1999. And this is more specific with opioid overdoses, which is our primary overdose of concern right now. And once again, the trend is certainly increasing and this is further delineated just by gender. And the provisional data, it's an increase in almost 30%, and this is up to 2021. 2022 is finalized and they're looking at 2023. Once again, these numbers are continuing to certainly increase. The current wave of our drug overdose epidemics is driven by deaths related to synthetic opioids, mostly right now fentanyl and other synthetic opioids. We're gonna do some foundational definitions in terms of our toxidromes. And we'll take a look at the classification of toxidromes. Generally, there's five common types that we look at to classify these groups. And the toxidrome is generally a group of signs and symptoms constituting the basis of diagnosis of poisoning. As you can see here, the five, the sympath, yeah, excuse me, sympathomimetic. I had practiced that in the mirror today for like 30 times, my apologies. Hallucinogenic, anachronolinergic, sedative, hypnotic, and opioid. And these, there is some variation with these, but these generally are the five classifications that we look at when we are talking about our toxidromes. As stated earlier, a toxidrome refers to a group of characteristics, signs, and symptoms that are caused by exposure to a particular class of drugs that act on a particular receptor. This typically leads to a constellation of physiological aberrations. So in layman's terms, these aberrations are specific to the toxic substance that we are seeing clinically and physically manifested in the body. The diagnostic and therapeutic approach to the patients with the suspected overdose. We're gonna have a systemic and consistent approach to these patients. We're gonna have a focused history and physical examination. We're gonna give supportive care. And we are constantly working in parallel. This isn't a X, Y, Z clinical exploration when we're looking for these toxidromes. We are often working continuously with the supportive care management. Our systemic approach, you would like to approach these patients in a consistent manner, generally when these patients come through, or if I'm seeing them in the emergency department for the first time, their standard EKGs, laboratory workup, BGs, ABGs, imaging if required, if the patient was found down, unresponsive, CT scans. If there's seizure activity, we're going to treat that seizure activity. All the time thinking about how we can work in parallel if there is a suspicion of a toxidrome or suspected overdose with the patients. When we start thinking that route, we're thinking about decontamination. We're thinking about antidotes for these medications, enhanced elimination, and or even continued with that supportive care as well. The next slide, which is also will be available in your concepts chapter book when you do receive it. This is a lot to process here. And this is the toxidromes and generally the physical signs that we may see from the toxidromes and the clinical and laboratory data as well. And some of the causative agents. We'll touch upon these a little further in the presentation here as well. But as I said, this will be available to you. And it breaks it down into what you may see with the mental status, hemodynamics, skin, pupillary reaction, other signs and symptoms that generally accompany these specific toxidromes, as well as some causative agents, which is important. And of course, what we are looking for in terms of our ICU needs. This further goes into the other two that were unable to fit on the previous slide. Excuse me, the opioid and sedative hypnotics as well. As I said, I will get into a little further specifics with these as we look to continue throughout our identification of the toxidromes. One of the other methods that we certainly do with our supportive care when we're evidence gathering with our patients is we send the urine drug screen or UDS as well. We generally send acetaminophen, salicylate, and ETOH levels if we don't know the story surrounding the patient or when they came in. And this is where we get to start playing detective as well. My experience has certainly shown that whether intentional or unintentional, there generally is not only physical and clinical manifestations that the patient may show us what they've taken, but there also is EMS at the scene that is very helpful in, they may have found empty pill bottles down, talking with family members as well. Sometimes, unfortunately, with the intentional overdoses, they call someone or notes are left and they let them know what they took or what they're intending to do as well. So this, the UDS, is an additional intervention that we generally send along to look at, to have confirmatory information presence of these drugs that may be available in our urine. Of note, one of the items that we want to look at that the, as you can see here, the detection time in the urine. Now, of course, this is not all the medications, but the detection time in the urine is certainly somewhat variable for medications. And that initial immunoassay that they do send, that shows us a recent reflection on exposure that does not tell us if the patient is intoxicated. So this is a very important distinction with these and the confirmatory immunoassay, the gas chromatography or mass spectrometry is highly specific to usually testing for a specific drug as well. So the specificity gets more aligned with the specific drug we're looking for. And that initial lets us know about presence, yes or no. I'll use myself an example. I am not, but if I came in and I tested cocaine positive, but I have a multifocal pneumonia with everything, that doesn't necessarily mean I have a cocaine induced toxidrome with those. So oftentimes we use this as a red herring sometimes and get blinded by the fact that we may have some positives in the UDS, but may not be impacting the patient and vice versa as well. Two important distinctions to keep in mind when looking at this. There are numerous medications that can falsely show up as presumptive positives as well. So the only, in the literature, the only one that I certainly was able to find in talking with my toxicology colleagues is cocaine. There is nothing that is going to say you ate the old poppy seed with bagels and you're testing positive for cocaine as well. So that one will not work. Just as I said here, does not measure the specific amount of drug present in the urine samples. It only provides a negative presumptive positive results with the immunoassay and then the confirmatory one is highly specific to testing for that drug as well. So our ICU admission, as I said, this generally for us, the majority of us, it appears that we do work in critical care is generally black and white when we look at mechanical ventilation. If the patient has the inability to protect their airway, they're profoundly acidotic, profoundly hypoventilatory, pneumonias, acute on chronic, all sorts of those modalities that will place the patient on mechanical ventilation. The cardiac toxicity or vasopalysia, these patients require, can require specific to some of the medications, a fair amount of presser support when they become profoundly vasopalysic. Certainly in some cases of metformin overdose and we'll talk a lot more about the cardiac toxicities on some of the specific ones that happen. Vasopressor and vasodilatory medications, some more intense neurological monitoring, continuous LTM, EEG as well. And some of the modalities that we do have available to us through ECMO, hemodialysis or CRRT as well. One of the extracorporeal elimination techniques that we can look at here is, this is a governmental website called Xstrip. It's a tremendous resource for the medications that can be eliminated through hemodialysis, CRRT, plasma transfusions. And just to name a few, these are your top, generally most prioritized medications that we can look for in terms of removal with dialysis, included, not up to all of them, ethylene glycol, metformin, lithium, methotrexate and salicylate as well on there. I just would like to make a mention of the ethylene glycol and the testing for ethylene glycol. Now, this is our toxic alcohols that we are generally looking at. And one of the approaches that I was always taught with any overdose patient is to send the serum and calculate and send the serum for an osmolar gap with these. There is increasing literature and evidence that detection of the osmolar gap, certainly it widely varies in the equation and laboratory that it's run. But the majority of these patients don't have the toxic alcohol poisoning that this many years ago had pointed to and said, yes. There's numerous influence on the serum as osmolar gap, renal failure, ketoacidosis, shock, electrolyte abnormalities, even contrast dye can all certainly influence that. The takeaway is that this is not solely one lab that we hang our hat on for this, but certainly can be used in adjunct when identifying potential ethylene glycol intoxication. And this, I have found that the more concrete evidence for this is the crystal urea that you'll see in the urine. You have the history of documented potential antifreeze ingestion is the big one with that anion gap acidosis as well through that. So just to mention to that, as I said, it is increasing in the literature in terms of the use for it. I think with the majority of items that we use that it is certainly a helpful adjunct in the right situation. Our toxic specific management, when we have stabilized these patients and we have gone through that broad umbrella of that supportive care for the patient, we're looking at these medications we're gonna put on our toxicologist hat if we can potentially do any GI decontamination for these patients. Is there any specific antidotes for these patients that we can use? Or is there enhanced elimination techniques for these patients as well when we are going through our differentials for these? Some of the interventions here, there's a, as I said, certainly widely more. Some of the more common ones that we may see in some of these patients is the intralipids, the 20% fat emulsion that you'll see. This is generally indicating the cardiotoxicity, the vasoplasia and more, well, some in the inpatient world, as well as local anesthetic systemic toxicity as well. And there are numerous theories on the pharmacokinetics and how this applies and works to the toxicology patient. One of the main ones is the lipid sync theory that can certainly change the dynamic in the blood and just as it sounds, act as a catch-all for the decrease in the plasma, ultimately reverting it back to lipids as well. Now that is probably the most simplistic explanation you're going to get without diving into the specifics of that. There's also some other theories called fatty acid metabolism, ion channel modulation, and nitric oxide. Knowing that the indication for this is generally severe cardiovascular collapse and the vasoplasia. The whole bowel irrigation. This is generally looked at for medications that the patient has taken that is in an extended release, the XL or ER, toxicity. And this is essentially an accelerated prep for a colonoscopy. Polyethylene glycol is generally run through the patient in one and a half to two liters an hour. If that sounds like a lot, it certainly is. And the premise of this is not to allow those bowels to have the chance or in the stomach to have a chance to absorb these medications as well. Oftentimes what happens with these patients without direction is they'll have emesis and then the whole bowel irrigation will be discontinued. And then they're like, oh, the patient's hemodynamically, we're getting better. Now they're getting worse again. We're having, if it's a tricyclic, we're having these widened QRSs again. They're hemodynamically unstable. That's allowing the bowel for these to start to absorb these medications as well. So the recommendation is if there is emesis, generally the flow of the glycol is reduced by 50%. These patients can be intubated. If they are, you do have that secure airway as well. Charcoal decontamination is a, I'm sure everyone has at least heard of this. The charcoal is best when you have a known immediate post-ingestion period and it works most efficiently within one hour. Now the reality is how many times we see those patients with that, less likely for that. And this, the charcoal is the binding agent to excrete these and not to allow for that medication once again to absorb. The inhibitive process of administering this, once again, is that timeframe for it and the indication for the medication as well. We also have high dose insulin infusions, generally indicated for medications that we may cause PICS, poison-induced cardiogenic shock for patients. And these insulin infusions, generally for our classic calcium channel blockade or beta blockade for patients, it improves cardiac mile site function, direct ionotropic effects, and increased glucose transportation for these types of patients. So that is indicated in the patients with severe beta blocker or calcium channel blocker overdose. And more specifically for the beta blocker overdoses as well, we will look for glucagon for these patients, which also can have a host of effects as well. And once again, we have some enhanced elimination techniques for them as well as physiostigmine and fimepazole that we look to do with patients. That we will find these patients with the anticholinergic overdoses that will inhibit the anticholinergics in the patient, as I said, with the tricyclics as well. Now we will get into some of the medications that we're seeing for the drugs of abuse. And not limited to these toxidromes, the anticholinergics, the tricyclics, the SSRIs, NSSRIs, Benadryl that we'll see, opioid. We're seeing kratom, fentanyl, oxycodone, heroin, hallucinogenics. We're seeing ketamine, the sympathomimetics. I got it that time, nailed it. Cocaine and methamphetamines and sedative hypnotic ethanol as well. One of the ones I'm going to look to and show first that we have seen. Now the majority of these medications you will see have some geographic distribution and prevalence in different areas. This is one that we are starting to see more of in upstate New York. Xylazine, also known as Trank on the street. It's a non-opioid veterinary tranquilizer. The pharmacology of it, it's an alpha 2 adrenergic agonist. It's generally used for anesthesia and sedation for farm animals, mainly horses as well. And I have a few colleagues who are, that breed horses and race horses as well. And just it was discussing this with them and talking with them. They have refrigerators full of this stuff, which is a little frightening sitting out on their farms or in the houses as well. But certainly getting locked up now and veterinary and those sorts of things as well. So the prevalence and the accessibility is certainly out there. Clinical presentation that we generally see with these patients is respiratory depression, bradycardia, and hypotension, which can be a lot of the clinical signs that we see with the majority of these medications with these patients. It's associated with higher fatality rates. This medication, like most of the toxidromes you see, certainly overlap with one another, which makes it difficult at times to pinpoint one. And that's when we go back to our foundational more of that umbrella, critical care and seeing through. I was going to give a photo disclaimer, but after seeing those trauma ones, I don't think it's necessary. So this. So one of the items that we do see with these types of medications as the xylosine is the skin necrosis, unfortunately. With this, patients will come in with use from this. And this is caused by basal constriction at the ulceration site. And once again, as I said, it's often with co-ingestions. Reversal agents exist for farm animals, not for human or FDA. One of the things that if this is suspected or the patient is telling us this, we will still or EMS will still out in the field administer naloxone or Narcan, just given the fact that it generally is a co-ingestion. So you could at least take care of that opioid piece as well. These necrosis are, of course, you can see here are not benign. Generally, our wound consult consults, our burn may be involved team for the specialist, as well as plastic surgery for these of note. We unfortunately had a patient that was running out of spots to inject into and had two very large ulcerations that unfortunately necrosed into his major vessels because he was injecting into his IJs at that time. So not a benign medication by any means. The next medication that we're starting to see more of is kratom. This is available certainly where we are. I probably see on my way into work, probably four or five signs in our city where this is available and can be sought out. This is a tree native to Southeast Asia, and its products are derived from its leaves that are marketed as herbal supplements. And it contains chemical compounds known as alkaloids. And of course, it's currently legal in the U.S. It is on the FDA most watched drug list moving towards not being legal at this time, as well as the DEA list in turn. Generally sold as a tea and powder. It's used, has analgesic and opioid effects. This I found, and this is why it's abused, it has the infinity for the opioid receptors, 13 times that of morphine as well. So you could see why this is readily available, readily accessible, that people are buying this and abusing this medication. Low doses, it acts as a stimulant. Higher doses, opioid toxicity. Co-ingestions are certainly in common, and cardiac, hepatic, pulmonary, renal toxicities, this can affect a multitude of organ systems as well. Once again, not a studied role for Naloxone, but if it does progress, sometimes through hepatic shock or hypoxia, that there have been studies supporting mucumus or acetylcysteine for this as well. Our next one, I believe we are all probably familiar with, the opioid toxidrome morphine codeine, which are derived from the opium poppy. Oxycodone or heroin, heroin for in our area, probably four or five years ago was the major player, now it has transitioned to fentanyl, and almost solely transitioned to fentanyl with the co-ingestions as well. Isotadazidine, close, sorry, apologies. This is also a new, fully synthetic that is even more potent than fentanyl that is gaining some attention as well across the United States. Since 2021, nearly all opioid overdoses have involved fentanyl. Just did a quick anecdotal prelim study, laced with cocaine, nearly 95% of our cocaine overdoses are also testing positive for fentanyl right now as well. And I'm sure that number is even going higher. Of course, driving mortality with this is the respiratory depression, ensuing hypoxia and hypercarbonyl, oftentimes when these patients are found, if they are found in a relatively safe amount of time, and I use that word loosely, they have already sustained an anoxic brain injury, HIE, and it is a long course for them if they do prove to be in a vegetative state, vent dependent, G-tube dependent, those sorts of things as well. And oftentimes, sometimes these patients don't even make it, unfortunately, to us. Naloxone, I'm sure everyone has heard of this. Opioid antagonist, competitively binds to the mu receptor, this is our antidote for the reversal agent for opioid intoxication, can be induced nasally in the field. And now, unfortunately, we are, this is becoming more readily available at Walgreens or any pharmacies for patients to have on hand. If repeated dosing is necessary, they may require naloxone infusion, this is generally, of course, when they come to the ICU for us as well. And this is also where we need to figure out if we can, if the patients can talk to us. My experience has been the majority of these patients are very willing to tell you what they took and how much they took, and if we do have some confirmation of that, we can certainly look at the amount of what they took and have an idea of the pharmacokinetics with that. And what I mean by that is have an idea of what this half-life is and what the expectation may be. They may be, I took 20 oxycodone pills, or I took the extended release pills, and then from there, we can figure out how long they may require the naloxone infusion with that. There are adverse effects with the administration of naloxone, mainly pulmonary edema. We can induce withdrawal symptoms and aspiration, of course, as well. And throughout this, we are going to support the oxygenation and ventilation for the patient. The anticholinergic toxicity, this is the fun one, they say, so to speak, because the mnemonic for it, people haven't heard this, red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hair, full as a flask. This is one that encompasses both CNS and peripheral manifestations. This one, if not caught early or identified early, can lead to a very high mortality. And this is not up into including antihistamines, antipsychotics, and antispasmodics, as well. And so, with this, what you see, just as the mnemonic says, these patients have flushing of the skin because they have vasodilatory effects. They are not diaphoretic. They are very dry. They have pupillary dilation, blurry vision, delirium, hallucinations, seizure, confusion, bizarre behaviors, as well, and full as a flask, could be urinary retention, as well. This is very similar to serotonin syndrome that we'll see in patients, the sympathomimetic overdose. However, a key distinguishing feature is the absence of diuresis. So, that's the big distinguishing feature between serotonin syndrome and anticholinergic toxicity. We're going to use sodium bicarbonate. If we see, we're going to get serial EKGs for these patients. Oftentimes, the potassium and sodium channels have cardiac toxicity. We have lengthening of those QTC and QRS monitoring for these patients. If caught early, we can do the decontamination with the activated charcoal, as I mentioned earlier. This was more of a whole bowel irrigation for one of the patients that we found that did take the extended release for this. Oftentimes, just through the agitation alone with these patients, if they did have some component of rhabdo, it can certainly make it worse. And the hyperthermia, as well. And physiostigmine, once again, inhibits the acetylcholinerase by increasing acetylcholine through that. Ketamine is another one. In the absence of time, I'm going to, this is certainly available to you and through our book chapter, as well. We're seeing this on the street, often used with other medications. Generally, don't have acute decompensation with this. Once again, that supportive care. But the issue is the administration and the lasting effects of the other medications that this is generally used for, as well. One thing of note, emergence phenomenon can be complicated with ketamine, even with general anesthesia, or procedures, as well, which can certainly complicate an overdose picture for these patients. Here's our chart, once again, for our overview of sedative hypnotics. I'm going to take 30 seconds to alcohol withdrawal. So this one is probably one of our more common ones, I'm sure, at least, once again, if we had to do a show of hands, 95% of the people in here have taken care of a patient with alcohol withdrawal. And just through my own, once again, anecdotal experience, I think, in our medical ICUs, which we have three of them, certainly post-COVID, this has taken off even more in line with cocaine and fentanyl, as well. So what we want to keep in mind for the alcohol withdrawal for these patients is we want to have the ability to recognize when they are going into potential DT, delirium tremors. The alcohol withdrawal itself, when these patients are potentially going into withdrawal, and the timeline for that, which can generally happen 6 to 12 hours. Seizures can happen 12 to 48 hours, as well. And the DTs are generally 24 to 48 hours out with that. And we are going to treat this as if we would anyone else with hallucinations, in terms of the benzodiazepines. Librium is one. We use more of phenobarbital. We have a whole protocol for that at our institution. I know all the institutions are a little bit different from that. Oftentimes, these patients often require a protected airway because of the amount of medications that they do receive. In addition, we'll look out for any nutritional deficiencies. Wernicke's prophylaxis. We'll do high-dose thiamine for these patients, as well as folic acid. In turn, with that. All right. Early recognition. Identification of the toxidrome. Presenting clinical features. Diagnostic and therapeutic interventions. These can often overlap. As I said, once again, we're always working in parallel to identify these toxidromes. And there's a multitude of resources out there for you, depending on where you are, in terms of treatment for these patients, as well. Thank you. Go Bills.

toxidromes

patient care

ICU admission

clinical signs

interventions

drug overdoses

naloxone