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SCCM Pod-503: Current Concepts: Toxidromes and Illicit Drug Abuse In the ICU

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This is the third episode of SCCM’s Current Concepts Series, in which authors unveil exclusive insights into the 2024 Current Concepts Course. Diane C. McLaughlin, DNP, AGACNP-BC, CCRN, FCCM, is joined by Aaron Goodwin, PA-C, MS, and Brett Hogan, ACNP, BSN, MS, RN, to discuss updates in toxidromes and illicit drug abuse in the ICU. The guests explain why this is an important topic and share their surprising discoveries while researching the topic.

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Disclaimer: This educational activity is supported by the SCCM Current Concepts Committee.

Dr. McLaughlin: Hello, and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Diane McLaughlin. Today, we’re joined by Aaron Goodwin and Brett Hogan in the third episode of our multipart series introducing the Current Concepts course and text. Get ready to dive into each chapter as we chat with the authors, providing an exclusive sneak peek into their expertise in the course content.

Aaron Goodwin is a physician assistant and adult critical care education coordinator, and Brett Hogan is an acute care nurse practitioner at University of Rochester Medical Center in Rochester, New York. Welcome, guys. Before we start, do you have any disclosures?

Mr. Goodwin: This is Aaron. Pleasure to be here, and no disclosures.

Mr. Hogan: Hi, Diane. Thank you for having us. This is Brett, and I also have no disclosures.

Dr. McLaughlin: Okay. Great. Today, we’re going to be diving deep into the world of toxicology in the intensive care setting. From accidental overdoses to intentional poisoning, understanding toxidromes is critical to saving lives. But before we go any further, for our listeners who may not be familiar, can you briefly explain what a toxidrome is?

Mr. Hogan: For sure, Diane. A toxidrome is a syndrome generally caused by a dangerous level of toxins in the body, often a consequence of a drug overdose, which we’ll discuss shortly. It’s classified into five different common types.

Dr. McLaughlin: All right. Can you share with us what makes this topic a current concept in critical care?

Mr. Goodwin: Yeah, Diane. I think everybody who works in critical care has seen an increased prevalence over the last few years in both intentional and unintentional overdoses, which do contribute to very specific toxidromes that we’ll talk about a little bit later. Just to put some kind of grim numbers on the topic, some CDC data say that, since about 1999, we’ve had almost a million overdoses; the numbers have grown exponentially over the last few years. Particularly during the pandemic, the numbers have started to escalate with an increased prevalence of opioid overdoses, including some novel synthetics.

Dr. McLaughlin: If we start at the beginning and, just for instance, I work in neuro and we had a patient come in with seizures, a lot of metabolic derangements, and we thought there was some type of ingestion or overdose, and it was days later until we found out what it was that the patient took. What do you do when you get these patients and you don’t really know where to start? Where’s the best place?

Mr. Hogan: That’s a great question, Diane. This is how, when we did approach this chapter and the information that we have provided in it, it was to hopefully answer and guide that question for any clinician or provider. The first item that you want to keep in mind is a systematic and consistent approach to all of these patients in terms of the ABCs and prioritizing. From your example that you had said, still not forgetting about if the patient’s septic, if they have some head injury, or whatnot. When you approach these patients, there’s a series of labs that we usually look for and also gathering the information surrounding their presentation in terms of what was found at the scene, collaborating with family or friends, if they have any information that may be helpful, talking with EMS, as well as looking at identifiable prescriptions or anything that they did have available to them.

Dr. McLaughlin: So it’s really supportive care while you play detective.

Mr. Hogan: Yeah, that’s a great way to put it. The majority of this, until we can certainly start honing in on some of these toxidromes and the specific overdose medication or drug that they took, is certainly that—supportive care—until we can get more specific.

Dr. McLaughlin: Let’s look at these toxidromes individually, starting with sympathomimetics. What are some common agents that fit in this group?

Mr. Goodwin: Some common sympathomimetics that we will see patients present with would be cocaine, methamphetamine, or MAOIs.

Dr. McLaughlin: Then, what do these patients look like on presentation? Is there anything unique to this group?

Mr. Goodwin: Yeah, these patients usually come in, when you think of sympathomimetic toxidrome, they’re usually somewhat agitated, they’re usually tachycardic, they may be hyperthermic. One thing that will differentiate a sympathomimetic toxidrome from another similar one in anticholinergic will be they will typically be diaphoretic as well. And usually the most common presenting complaint is related to their agitation.

Dr. McLaughlin: Is there anything specific for a treatment protocol that’s different in this group?

Mr. Goodwin: The treatment, like most toxidromes, is generally supportive. Benzos, the first line for agitation, are a good place to start. You could also consider an antipsychotic as needed. The other considerations would be that, specifically, hyperthermia should be monitored and controlled as needed. And controlling the agitation can sometimes prevent any unwanted rhabdo symptoms that may present. The one thing that I’m sure everybody is aware of in the literature is the mixed data on beta blockade use, specifically regarding cocaine, that is one point that I think clinicians should be aware of.

Dr. McLaughlin: Wait, so is that an old wives’ tale? The thought is that you can’t give beta-blockers because of unopposed alpha activity. Is that right?

Mr. Goodwin: Yeah. I think that is what there have been a few case reports about. There have not, at least in the literature searches I’ve looked at, and we included in our chapter, that looked at any mixed alpha and beta blockade, no adverse events reported with mixed beta blockade, but that is the common wisdom with unopposed alpha.

Dr. McLaughlin: So would you use a beta-blocker if you needed to?

Mr. Goodwin: I think, in the right clinical setting, everything should be considered. But by and large, if it’s tachycardia in the setting of a cocaine overdose, unless there is a significant amount of tachycardia-induced ischemia, I would probably avoid that.

Dr. McLaughlin: Okay. So, interesting, you tolerate a little bit of tachycardia in these patients.

Mr. Goodwin: Exactly.

Dr. McLaughlin: Okay. Cool. You mentioned anticholinergic toxidromes. Do you want to speak a little to that? What medications? I think we all know anticholinergic agents, but anything outside of over-the-counter medications, and then how do they present?

Mr. Hogan: The anticholinergic classification, generally, it’s your antihistamines, your muscle relaxers. There’s certain antiparkinson medications that are in this group. The presentation for them, as Aaron alluded to, is somewhat opposite of the sympathomimetics; they’ll present as red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask. That is a saying that is used, how these patients generally present. Of clinical note, they generally look similar to patients who could potentially present with serotonin syndrome, but the key differentiation in this is that they are not diaphoretic, they are very dry.

Dr. McLaughlin: Can you please say that little rhyme one more time? I’ve never heard that before, so I just want to remember it.

Mr. Hogan: It’s red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask.

Dr. McLaughlin: Please tell me you thought of that.

Mr. Hogan: Oh, no. I cannot take credit on that one.

Dr. McLaughlin: All right. So, anything different with treatment in these patients?

Mr. Hogan: Once again, certainly going back to the priority with the supportive care. But if agitated, benzodiazepines are your first-line treatment and also collaboratively looking at controlling environmental factors such as their temperature, we are looking and monitoring for rhabdomyolysis as well and clinically looking for the potential QRS prolongation that these medications can certainly induce.

Dr. McLaughlin: How much of these medications do you really need to take to develop a toxidrome?

Mr. Hogan: With that, the amount of medications is going to vary independent of the patient and also in terms of if and how long they’ve been prescribed these or taking these, as we all know, jokingly, everyone fits into the same mold in medicine, which they do not. And it’s in terms of any specific medications that we have to look at. There are some levels that we can look at in urine drug screens that we certainly go into more detail in the chapter and some tables that can provide more concrete information of what those toxic levels are for the patients.

Dr. McLaughlin: Now, we know there’s been a rise in opioid-related cases, especially with some of the new agents out in synthetic drugs. How do we handle these cases?

Mr. Goodwin: Yeah. I think our experience here in our setting is heavy exposure to opiates, either intentional or unintentional intoxication. Some of that has changed, honestly, very recently with the emergence of similar drugs, specifically xylazine, that have been mixed into the street supply. Your initial treatment is going to be very similar to that of the other toxidromes with good hemodynamic and airway support, with the exception that these patients typically, depending on the degree of overdose, do have a reversal agent with naloxone that can help to stave off intubation and respiratory arrest. That should be considered pretty early in their workup.

Dr. McLaughlin: Does that work with some of these new medications? I know you can actually search online if you don’t have a prescription or don’t have access to even like a street dealer. So there are these medications that we don’t know anything about that people are importing. Would you still recommend using Narcan if you don’t really understand what the medication that they ordered or consumed is?

Mr. Goodwin: Yeah. I think if the patient is showing signs of decreased respiratory rate, the downside to using naloxone is relatively low, especially if used appropriately. In the opiate-naive patient, the likelihood of inducing a withdrawal syndrome is pretty low. In a chronic opiate user, the likelihood of inducing withdrawal syndrome is higher. However, if it is judiciously titrated to effect, which is really just improvement in respiratory drive, not wakefulness, then the likelihood of a withdrawal syndrome is much lower. Rarely, naloxone has been reported to induce some pulmonary edema as well, but that is pretty rare and would not outweigh the benefit of giving it to somebody with an impending need for intubation.

Dr. McLaughlin: That’s actually really interesting, because we were trialing Narcan for the prevention of neurogenic pulmonary edema following brain death. It just tells you all of these medications can do pretty much anything and you just really have to know them. It’s shocking to me how many people in the ICU have never actually administered Narcan. Are there any tips that you can give to our listeners?

Mr. Goodwin: Yeah. Actually, this is a tip that Brett taught me when I was starting off in the ICU many, many moons ago. This is the way I prefer to personally titrate naloxone. It usually comes, at least in our facility, it comes in 0.4 mg per 1-mL vials. What I like to do is to reconstitute that by wasting 1 mL of saline and drawing up that 1 mL of naloxone in that 9 mL of saline, thereby diluting it 10 times. Then I will administer a few cc’s at a time, essentially giving a tenth of a dose at a minimum until we get a stable respiratory drive. You can usually find a happy medium in a much lower dose than you would have otherwise given where you don’t induce a withdrawal but you still have a good respiratory outcome.

Dr. McLaughlin: That’s a great tip. That’s actually how I was taught as well. Just a cc or two at a time after you reconstitute into the 10. It’s funny, the people who give the full concentrated dose, a lot of these patients, it’s like waking the dead and pretty shocking for people who haven’t administered it before. But sometimes, if you stop administering it, an hour or two later, sometimes not even an hour, these patients can redevelop respiratory depression. Do you guys ever use continuous infusions?

Mr. Goodwin: Yeah, we do use continuous infusions when repeated doses are necessary, and one thing that is talked about in the chapter as well is there’s a novel agent that was just granted FDA approval similar to naloxone called nalmefene, but it will last significantly longer than naloxone when you do achieve full reversal. It can last up to 12 hours so that can usually bridge you through that recurrent period. It’s just not widely available, and we don’t have it here in our institution.

Dr. McLaughlin: That’s interesting to know, another reason why this is a current concept, teaching us some of the things that are just new and coming. Let’s talk a little bit about sedatives and hypnotics. Which medications or street drugs would you consider part of this group?

Mr. Hogan: Certainly, we have some of the more likely common overdoses that we may see, mainly alcohol, EtOH, as well as some of the newer ones that we’re finding, xylazine, also known as tranq, which is generally prescribed by veterinarians but certainly has unfortunately gained more exposure and accessibility on the street as well.

Dr. McLaughlin: Then, I know you’re going to say supportive care, but any specific antidotes to any of these agents that everyone should know about?

Mr. Hogan: Certainly, it may be a sort of review for the majority of people, but certainly with the EtOH intoxication that we always have to be mindful of, depending on when they come in, the amount they drank, looking for that timeline of potential withdrawal and/or having hallucinations and seizures and the delirium tremens that we see with that type of intoxication. Along those lines, also looking to provide Wernicke prophylaxis with thiamine and folate in that period as well. But generally, for alcohol withdrawal, the benzodiazepines are typically considered first line. Now here at our institution, phenobarb has been increasing certainly in usage and accessibility and does seem to work well with these patients.

Dr. McLaughlin: Now, you guys have worked in critical care a long time. Is there anything writing this chapter that really surprised you?

Mr. Hogan: For me, the surprising thing throughout, looking at this and working with Aaron and Katie, one of our other colleagues, who was unable to make this, that the amount of information that is out there can be very daunting. And as we alluded to and stated earlier, that there’s multiple avenues and adverse effects from medications and what they’re used for. I think that was one of the most challenging things for me and eye opening. As I stated that we try to direct this information so you can take care of the overdose patient and have an algorithm that would be useful and applicable to this patient population.

Dr. McLaughlin: Other than buying this book and attending this course, are there other resources that are readily available that you recommend people be familiar with when treating patients who present with suspected ingestion or overdose?

Mr. Goodwin: Yeah, I think, Diane, to your last question, one thing I would add to what Brett said is that this course and this chapter is really putting patients into five nice, neat categories, which the vast majority of patients who present with some degree of a toxidrome rarely fit into one pure category. So understanding that the patient who has probably some degree of anticholinergic toxicity may also have other agents on board that may benefit from things like phenobarb if there’s a degree of benzo involved or just the fact that most toxidromes and overdoses do not come as a sole agent.

I think there are a lot of good resources available online. I hope that this chapter does provide a lot of good resources to patients. I think, for very specific overdoses, we have the luxury here of a toxicology service, but patients or clinicians nationwide may actually use their local poison control center as a good resource as well.

Dr. McLaughlin: How would you apply the most recent evidence into your practice? Has your practice changed since writing this chapter?

Mr. Goodwin: I’ve noticed a significant change here in our community in the last year, specifically with a massive increase in fentanyl overdoses. And the recognition, I think, by myself and the local community here of an increased prevalence in xylazine as well. That’s one thing that I think we see the most of. I think that’s the biggest change to my personal practice.

Mr. Hogan: And for my practice, it’s certainly still working collaboratively with our toxicology colleagues, but for my own knowledge base as well being more readily identifiable in terms of their clinical presentation and/or the adverse effects of the overdose and looking to potentially get some antidotal medications in place earlier, some lab draws as well. So, just being cognizant and having a wider array of potential interventions available to the patient.

Dr. McLaughlin: I’m lucky that I got a sneak peek at this, because I know this probably isn’t going to be shocking to you, but I’m a little bit naive to what’s going on in the community in terms of drug use or substance use. There are things that I’ve never even heard of, like, what is it, kratom?

Mr. Hogan: Yes. KRAT-um, KRAY-tum, that is unfortunately sold in tea shops as well as corner stores and on the street, it’s very readily available, that can mimic some of the analgesic properties of our medications out there. Unfortunately, abusing it can certainly cause respiratory failure, renal failure, rhabdomyolysis as well.

Dr. McLaughlin: Just talking to you guys and reading your chapter in preparation, there’s a lot more that I’ll be watching for or putting in the differentials that, honestly, I didn’t even know existed. So I really appreciate you guys writing this.

Mr. Goodwin: Thank you.

Mr. Hogan: Thank you. Yeah, it was a great experience for the three of us as well, and we’re excited to have this out there and continuing the educational aspect of it.

Dr. McLaughlin: I think my last question for you is going to be, is there anything coming, anything pending about the topic that might emerge in the next few months or years?

Mr. Hogan: That’s a great question. Just as we’ve seen anecdotally after COVID, the amount of overdoses and some associated mental health crises that we’ve seen with these medications, as Aaron alluded to earlier in the discussion, that right now we are seeing a majority of fentanyl and cocaine, and xylazine as well. And I’m amiss to say this, but unfortunately, there will be another drug that will be coming on the street that we would think of how to abuse.

Dr. McLaughlin: That actually is very disappointing to hear.

Mr. Goodwin: Yeah. In fact, doing a lot of the research for this chapter is another one we haven’t mentioned yet, isotonitazine. Another one that I was completely unaware of before writing this chapter that is another synthetic opioid that has popped up in various clusters through Europe and the U.S. that unfortunately, that’s most likely going to be the more current change, is more and more synthetic opiates.

Dr. McLaughlin: In conclusion, I’m hearing to have a high suspicion for different agents based upon the presentation, that supportive care is paramount, and then utilize your resources for targeted treatment. Does that sound about right?

Mr. Goodwin: Yeah. Exactly.

Dr. McLaughlin: This concludes another episode of the Society of Critical Care Medicine Podcast. For more on Current Concepts, please listen to the series. And don’t forget, if you’re listening on your favorite podcast app and you liked what you heard, consider rating and leaving a review. From the beautiful shores of Lake Ontario, for the Society of Critical Care Medicine Podcast, I’m Diane McLaughlin.

Disclaimer: This educational activity is supported by the SCCM Current Concepts Committee.

Diane C. McLaughlin, DNP, AGACNP-BC, CCRN, FCCM, is a neurocritical care nurse practitioner at University of Florida Health Jacksonville. She is active within SCCM, serving on both the APP Resource and Ultrasound committees, and is a social media ambassador for SCCM.

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Knowledge Area: Pharmacology