I am an acute care nurse practitioner at the University of Rochester Medical Center at Strong Memorial Hospital, and today we will be discussing toxidromes and illicit drug abuse in the ICU. I have no actual or potential conflict of interest in relation to this presentation. Our objectives for this presentation are to offer guidance to providers to recognize patients with the most common toxidromes and understand who may require intensive care unit admission. We will look to summarize the most up-to-date evidence, how to stabilize, treat, and prevent complications of various toxidromes of patients admitted to the intensive care unit. The U.S. is struggling with a drug overdose epidemic. Accidental and intentional poisoning from both illicit and illicit substances remain a major cause of morbidity and mortality worldwide. To further evaluate the data, the overdose deaths mainly primarily caused from opioids The most current wave of the drug overdose epidemic is driven by deaths related to synthetic opioids such as fentanyl and its analogues. Let's turn our attention to the definition of what a toxidrome is. A toxidrome is a group of signs and symptoms constituting the basis of diagnosis of poisoning. Five of the most common types of toxidromes are sympathomimetic, hallucinogenic, anticholinergic, sedative-hypnotic, and opioid. Further to define a toxidrome refers to a group of characteristic 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 that can help healthcare professionals identify the likely toxic substance involved and guide appropriate treatment. That last key part of the definition for toxidrome, the aberrations can be specific to the toxic substances involved, will be something that we will continue to focus on and take priority throughout the rest of the presentation. Next, we will take a look at the diagnostic and therapeutic approach to the patient with the suspected overdose. This generally contains a constellation of these four pillars. We will look at systematic and consistent approaches to the, quote, standard workup for these patients on presentation, a focused history and physical examination, supportive care management, and in parallel, we will be looking to identify the nidus for the toxidrome. Generally our standard workup to these presentation of patients will obtain comprehensive metabolic profiles, laboratory data, blood glucose levels, EKG, any imaging, if warranted, if the patient was found down unknown or unknown amount of time, we may get some CT imaging of the head as well as chest, if applicable. We will also look to send routinely acetaminophen, ETOH, and also salicylate levels for the patients. The physical examination piece and supportive care management, we will look as always to maintain our ABCs, so if we are, patient is presenting as abundant or may have come into your institution already with a breathing tube in place, we will look to support that In addition to if the patient is hypotensive or has any tachyarrhythmias, we will look to abate those with fluids and or pressors. In addition to looking at, mentioned earlier, the EKG, paying particular attention to the QRS and QTC potential prolongation through our lab findings, we will look to evaluate for acute renal failure, hyperkalemia, and potential requirement of dialysis. Same can be said for if there is seizure activity, we will look to treat that with benzodiazepines and our standards of care for that. While we are treating for this, as I stated earlier, we will continue to look, working in parallel, and look to identify the nidus for the toxidrome. So we will continue to be thinking about toxic specific managements in terms of decontamination potentially, anecdotal medications for what was ingested, potential enhanced elimination techniques such as hemodialysis and or ECMO, in addition to maintaining that supportive care role. As we continue with the diagnostic and therapeutic approach to the suspected overdose, this is table one that is also included in your guidebook. It's the presentation of common toxidromes. What you will see here is I will spend a fair amount of time in terms of if we are concerned for a sympathomimetic overdose, an anacholinergic overdose, as well as a hallucinogenic overdose in the other two, is that there are specific presenting physical findings generally for these toxidromes, but we must also keep in mind that these toxidromes often overlap one another and they generally do not fit into one standard category alone. As we continue with our workup, we're adding the tox into the differential diagnosis. What are the expected toxic effects of the known or suspected substance? Does our clinical presentation match up with or meet the criteria for the toxidrome? We also will keep in mind the pharmacodynamics as well as the pharmacokinetics of these potential medications and adjustments, especially the durations of effects. An example being an extended release medication can certainly take a longer period of time to be metabolized in the body. If we are able to know what the patient took, we can at least give a anticipated time frame of clearance of that medication. Before we turn our attention to some additional testing, the urine drug screen, toxicology screen testing, I'd like to take a moment to also talk and discuss the ethylene glycol poisoning. If we suspect this, generally we calculate the serum osmol gap and I wanted to make mention of this because this is one of the more routine laboratory data sets that we do send to see what the osmolar gap is. The differential of the elevated serum osmol gap can be broad. It can include uremia and ketoacidosis, shock, and of course elevated levels of toxic alcohol. The ethylene glycol intoxication is generally based on a history of antifreeze ingestion, anion cap acidosis, and crystal urea. I have not had the elevated serum osmol gap. Certainly cracked the case in terms of differential diagnosis, but can be used as an adjunct for further supportive evidence. Of course, this test is usually sent when we suspect this type of toxic ingestion and it indicates the presence of solutes in the serum, which serve as a rapid surrogate test. Once this is sent, generally associated with the extended alcohol panel, we will find in the literature supports, most patients do not have toxic alcohol poisoning. Once again, the influence on the serum osmol gap is precluded by a number of factors including renal failure, ketoacidosis, shock, electrolyte abnormalities, and even contrast dye. And the detection of the serum osmol gap can vary widely on the equation and laboratory techniques used. My purpose of this and identifying this is that you take away that the literature evidence is poorly supported at this time to say the patient has ethylene glycol poisoning on one sole laboratory finding alone. With that being said, this can be used as an adjunct to help prioritize and come to the conclusion of potential ethylene glycol poisoning. Along those lines, the urine tox screen is also one of our standard workups that is sent. As you can see from the graph here, we have the detection time for a host of illicit and illicit medications on the left and the general time that they can be detected, the initial immuno assay on the next column and confirmatory immuno assay. The urine tox screen can be helpful in terms of a positive result may reflect a recent exposure rather than an acute intoxication. We need to interpret the correct clinical and historical context. For example, if the patient comes in and is presenting with tachycardia, shortness of breath, increased work of breathing, and hypertension and has chest pain and potentially a low oxygen saturation and we support the patient by applying some supplemental O2. We're trying to abate the tachyarrhythmia, maintaining perfusion, and we send urine tox screen and it comes back positive for cocaine. Now this does not mean that the patient is acutely in or having a cocaine toxicity. The patient may have fallen off a ladder and has sustained a trauma from the fall that may explain all this. So once again, we need to interpret this in the correct clinical and historical context. The initial screening process of the immuno assay, the antibodies, does not measure the specific amount of drug present in the urine. It provides a negative or presumptive positive results. Once again, it is going to let us know if the drug is present. The confirmatory immuno assay, which is often performed by gas chromatography or mass spectrometry, is highly specific to usually test-tube for a specific drug. So the difference between the two that we must keep in mind once again, is the immuno assay provides negative or positive if the medication is there or not and the confirmatory immuno assay can further delineate and detect the specific drug. Keeping in mind that there are numerous drug interactions that can pose as positive tox screen that the patient may have taken per prescription and it is showing positivity in an otherwise potentially illicit drug. Next, we can look at our ICU admission criteria, knowing that this may be influenced in terms of your institution or what available or not available resources that you may have. Certainly, anyone requiring mechanical ventilation or mechanical ventilation would be certain criteria for the ICU to protect the airway, hypoxic or hypercarbic respiratory failure could be associated with potential trauma for that as well. Any cardio toxicities and basal metabolic toxins that may be present in the airway as well. Any cardio toxicities and basal palesia, this would include the use of vasopressors and vasodilatory medications to treat emergent hypertension or refractory vasodilatory shock in terms of cardiac basopalesia, which has known to include up to multiple pressors and can generally potentially have the patient on three or four pressors required to help maintain perfusion. This hypotension has also been augmented by the use of methylene blue, which is a potent vasoconstrictive medication which inhibits nitric oxide. And continuing along these lines, the vasopressor and or the vasodilatory management may potentially include the use of ECMO for refractory vasopalesia that has not responded to pressors and or methylene blue. Neurological monitoring, we can look at refractory seizures in status. They're requiring multiple infusions of potential benzodiazepines, antiepileptics, some interventional monitoring as the LTM or continuous EEG. And also our extracorporeal modalities such as hemodialysis, CRRT, and ECMO, which was mentioned previously. One of the more more common of the extracorporeal elimination techniques is hemodialysis and or CRRT, which is continuous renal replacement therapy. This is more specific to a host of toxicities not up into including ethylene glycol, metformin, lithium, methotrexate, and salicylate. These are probably the more common overdose toxicities that you will encounter that do require hemodialysis. And I just have included in here a website for the extracorporeal treatment and poisoning. These are guidelines that in fact will help guide you through the medications that generally require hemodialysis, how long they may require, and any other adverse effects that you may encounter. Next, we will turn our attention to the toxicology-specific management. This is often classified into three categories of GID contamination, specific antidotes, and enhanced elimination techniques. Some of the interventions that we have available to us is intralipids, 20% fat emulsion. This is generally reserved for and indicated in instances of cardiotoxicity, vasorefractory vasoplasia, and local anesthetic systemic toxicity, also known as LAST. There are a number of theories in terms of how pharmacologically the lipids help vasoconstriction and increase the amount of vasodilation. There are also theories of increased perfusion. some of these theories are known as fatty acid metabolism theory, ion channel modulation, as well as a lipid sink theory, which is more in terms of a scavenger of the fat emulsion, mainly scavenging those items that may impede perfusion, potentially nitric oxide, which can be very vasoconstrictive. We also have whole bowel irrigation. This is generally used in indicated for large ingestions of sustained release medications. It's essentially an accelerated prep for colonoscopy. We administer anywhere from a liter and a half to two liters an hour of polyethylene glycol. And the benefit of this is to decrease the amount of time that potentially the medication can absorb in the GI tract. One of the adverse effects that we can have with the large volume administration is emesis. If this is to occur, the recommendations are to decrease the amount of polyethylene glycol being administered. To completely turn off the ethylene glycol will essentially nearly have a rebound effect of absorption for those medications, especially those ones that are extended release. We also have charcoal decontamination available to us. This generally is indicated for ingestions that happen within one hour. And patients are presenting in having a normal mental status. The largest challenge with the administration of the charcoal is the timing. That generally, we see patients of unknown downtime and or ingestion time, which makes the difficulty in timing in administration of this. It is reasonable to potentially dose charcoal after induction and airway is secured in patients. If the timing is applicable, we often do not intubate the patient to give the charcoal. High dose insulin infusions are often seen in calcium channel blocker and or beta blocker toxicities. This infusion works by improving the cardiac myocytes, essentially producing inotropic inhibitors. Producing inotropic effects, which also have associated glucose transport and vascular dilation as well. This is generally administered with a bolus of one unit per kg, followed by a continuous 1 to 10 units of kg per hour for these. Glucagon is also another potential anecdotal medication for beta blocker overdose. There are a number of adverse effects, including nausea, vomiting, hypokalemia, hypercalcemia. And the additional adjunct that we have available to us for beta blocker overdose is milrinone, which also can increase myocardial secamp levels. Essentially, once again, exerting positive inotropic and chronotropic effects. We also have available to us physiostigmine, which is indicated for anticholinergic overdose. This is generally administered 1.5 to 2 milligrams slow IV push. And this is, if available, on the recommendation of toxicology or tox specialists for the administration of this. As well as femepizole, which is indicated for ethanol or methanol glycol poisoning. And it essentially inhibits the alcohol dehydrogenase for the patients. And we also discussed earlier some additional enhanced elimination techniques of HD and ECMO and the medications for those. Now we will look at specific drugs of abuse that we are seeing currently in practice and throughout the nation. Once again, our toxidromes, and we break down our specific medications included in each. This is the most prevalent ones. There are likely additional medications that are just not included on here at this time. But the anticholinergics, we have tricyclics, SSRIs, Benadryl, opioids, kratom, fentanyl, oxycodone, heroin, hallucinogenic ketamine we're seeing, psilocybin is also becoming more prevalent, the sympathomimetics, cocaine, and methamphetamines, as well as the sedative hypnotic ethanol is leading, unfortunately, that category as well. One we are seeing more and more in practice is xylosine, also known as Trank on the street. This is a non-opioid veterinary tranquilizer. The pharmacology is that this is an alpha 2 adrenergic agonist. Half-life on the medication is around four hours. Clinical presentation is often associated with respiratory depression, bradycardia, and hypotension. And it has been associated with higher fatality rates. This is a medication that is often used as a co-ingestion and not used alone. And the medication, I would like to just give you a warning. There is a graphic photo of a known adverse effect of skin necrosis, given the severe vasoconstriction that this medication causes at the site on our next slide. So you can see here where this patient has been injecting into their lower extremity. And as I said, this is also a sign that the patient is likely using the xylosine because these injected skin necrotic sites are pretty prevalent, occurring in the lower extremities, in the popliteal area, as well as the femoral area. And we've even had patients in the carotid area near the IJs as well come in with severe ulcerations. As stated, this is often a co-ingestant with opioids, benzodiazepines, and ethanol. Reversal agents exist, but not proven safe or effective in human studies. And just generally on our unconscious patient in the field, per EMS, generally first line of defense is to administer Narcan naloxone, which does not work on the xylosine. And yohibine and tolazine are the reversal agents in the veterinarian world, but as I said, do not and have not been tested in humans. Our next medication is kratom. This is from, this can be sold as a tea or powder. It is found in numerous tea shops, gas stations throughout the US. It is a tree that is native to Southeast Asia. And its products are derived from its leaves that are marketed as herbal supplementations. The kratom leaves contain many chemical compounds. And of course, the overriding issue with this that it is not regulated. So if you potentially think you are buying kratom at a certain dose or amount, it could have additional compounds and or other potentially toxic medications that certainly could be harmful for you. It's currently legal in the US. And it is, once again, unregulated and not FDA approved. It's used for analgesia and opioid addiction. The pharmacology, the affinity for the opioid receptors is 13 times that of morphine. Lower doses can act as a stimulant, higher doses as opioid toxicity. As many of these medications are that we are seeing, co-ingestions are extremely common. There can have cardiotoxic, hepatic, pulmonary, and renal toxicities. There is a role for naloxone in specific kratom overdoses. With that being said, on case studies, they have reported that higher increasing frequent doses of naloxone are needed. And there are even some case studies supporting an acetylene muco mist as well because of the potential hepatic toxicity that can be caused by this. Our next toxidrome we are going to look at, and once again, this is our most prevalent toxidome, unfortunately, at this time in the United States. Morphine and codeine, which are derived from an opium poppy. Oxycodone and heroin, which are semi-synthetic. Heroin, initially before fentanyl, certainly became more widely available and made in pill and powder form. We were certainly having an epidemic with. And unfortunately, the tides have changed to fentanyl, which is fully synthetic, as well as isotonatazine, which is also a more potent form of analgesia, which is also a fully synthetic medication. Since 2021, nearly all opioid overdoses have involved fentanyl. Driving mortality, of course, is our respiratory depression, ensuing hypoxia, and hypercapnia. And also, once again, that this medication is often taken in as a co-ingestion and or taken in unknowingly. Currently, we are seeing in our institution numerous cocaine-positive tox screens along with fentanyl, unfortunately, resulting in hypoxic ischemic injuries and producing patients that are in vegetative states, unfortunately, as well. The antidote for opioids is naloxone, which is an opioid antagonist. It competitively binds to the mu receptor and, of course, is the reversal agent for opioid intoxication. If repeated dosing is necessary, then consideration to a naloxone infusion, if applicable. Some adverse effects of naloxone administration that you can facilitate and enhance the withdrawal symptoms from blocking and inhibiting that opioid, as well as aspiration event for patients, given that their downtime certainly predisposes their risk for an aspiration or pneumonitis event, as well as pulmonary edema. And our supportive care throughout these, if required and not responsive to the naloxone infusion, is support the patient's oxygenation and ventilation throughout the Toxidrome period. This is where we try to fact find in terms of what medications were at the scene, are these extended release medications, how much the patient took to give us a guide to what we can expect for the metabolizing of the opioid. Our next Toxidrome is our anticholinergic toxicities. These are generally our antidepressants, antihistamines, and antipsychotics and antispasmodics. This is the mnemonic below that represents both CNS and peripheral manifestations, and it's red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full of a flask. Now if these are taken solely alone, then this is the classic mnemonic that these patients present with when they are in a toxic state. The red as a beet is the vasodilatory effects and flushing of the skin. The anhydrosis and lack of diaphoresis is the dry as a bone. You will have pupillary dilation and blurry vision for these patients given the blind as a bat. Mad as a hatter, you will also see or potentially exhibit seizures, delirium hallucinations, confusion, bizarre behaviors, and paranoia. And the hot as a hare, loss of temperature regulation. As I said, you are exhibiting anhydrosis, so you are not diaphoretic. And full as a flask, you will have urinary retention as well. To keep in mind, the anticholinergic toxidrome may present similarly to serotonin syndrome or sympathetic overdose. However, the distinguishing feature is the absence of the diaphoresis. So this is a very important point to consider when you are trying to place your patient in a toxidrome or an overlap of toxidromes. Keeping in mind the patient exhibits the anhydrosis for the anticholinergic toxicity. Oftentimes, these patients are often have associated cardiac toxicity with prolonged QTC intervals in which we administer sodium bicarb 4 and we have serial EKG checks. We can, if known timing of ingestion, decontaminate with activated charcoal and or whole bowel irrigation. Severe agitation can worsen rhabdomyolysis and hypothermia for these patients. And keeping in mind if the rhabdomyolysis is severe and such in causing oligarch renal failure that despite fluid resuscitation and CRRT that we have those modalities available to us. In addition, keeping in mind that oftentimes these patients with severe rhabdomyolysis can proceed to compartment syndrome and potentially often require fasciotomies and or if they have co-ingestions depending on their time down some of these fasciotomies have turned into amputations or a loss of limbs because of the positioning of the patient when they collapse or they become unresponsive. Physiostigmine can be administered anecdotally for the anacholinergic toxicity. This inhibits acetylcholinesterase that normally breaks down your acetylcholine receptors. This allows for accumulation at the muscarinic or nicotinic receptors. Hallucinogenic toxicity, this includes ketamine, phencyclete, PCP, LSD, as well as psilocybin and acute intoxication of the hallucinogenics generally have self-limiting toxic features. These oftentimes require just supportive care. If these are taking alone as a sole ingestion, the goal is to limit sensory input for these. However, if they do produce a acute clinical decompensation or exhibit this, once again, we are going to prioritize our ABCs. We can abate the psychomotor agitation with benzodiazepines. Psychotic features, we can administer some neuroleptic medications such as Heldahl. Of note, activated charcoal is generally not recommended given the rapid absorption of these types of medications for the patient. Keeping in mind as well, the pendant on the amount of behavioral issues, agitation or psychotic features, if we have to administer a large amount of benzodiazepines and oftentimes these patients can transition into requiring the breathing tube given the large amount of sedative needs required to control their behavior. Ketamine is a dissociative anesthetic with hallucinogenic properties. Over half of patients administered ketamine experience what is known as emergence phenomenon. This is demonstrated by agitation, confusion, potential violent behavior and or disorientation. This is often when the patient, as is states, is emerging from the ketamine and or is being metabolized. Recreational dosing of ketamine generally is between 75 to 300 milligrams. Knowing that smaller doses of ketamine often produce hallucinogenic effects which decrease alertness, alters perceptions and cause ataxia and nysticmus. Next, we're going to take a look at the sedative hypnotics. These are one of the more classic presentations and occurrences that we may see, mainly the alcohol intoxication for these patients. Generally, what is indicated for them is having known withdrawal times. This is something that you would like to know in terms of their alcohol level and their ability of their liver to metabolize the alcohol. Knowing that the withdrawal can start as early as six hours, hallucinations can potentially start in 12 to 14 hours, seizure activity 12 to 48 hours, and the delirium tremors as well two to four days. This is inclusive of seizure, hallucinations, tachycardia, diaphoresis and potential nausea and vomiting. For these patients, we often give them high-dose thiamine and folic acid for Wernicke's prophylaxis on them as well as benzodiazepines. If required to try to abate the withdrawal at our institution, we rely on phenobarb loading and infusions. If requiring airway protection and management, then we will move towards propofol as well. Repeated seizure activity, if they do have it, this is often abated by the benzodiazepines, but if they're continuing to have repeated seizure activity, then it is certainly recommended to have our neurologist colleagues involved. They may require anti-epileptics as well as additional seizure workup for them. And you can see as included in the work study guide as well, table 5 does outline alcohol, benzodiazepines, and even barbiturates in terms of our workup for them and treatment as well. And generally of note, like many of the other ingestions, alcohol is oftentimes a co-ingestion for the patient. And keeping in mind that some of these presentations that we want to keep our differential broad and open mind that they may mask signs of hemorrhagic, cardiogenic, and or distributive shock as well. Our next category is the sympathomimetic. These include cocaine and methamphetamines. The presentation with the patient generally has tachycardia, hypertension, hyperthermia, agitated delirium, pupillary dilation, often adverse effects of this intoxication can include myocardial infarction, aortic dissection, hypertensive urgency, arrhythmias, diffuse alveolar damage, and hemorrhagic alveolitis. This is often caused by inhalation injury and smoking, rhabdomyolysis, seizures, and stroke. IV abuse of these medications can certainly predispose the patient to endocarditis, septic emboli, and bacteremias. Keeping in mind cocaine in a lot of the case reports and literature is often associated with rhabdomyolysis, which we had stated earlier can potentially lead to compartment syndrome, fasciotomies, renal failure, and potential amputations. The literature is unclear why this causes rhabdomyolysis. Some of the leading theories are cocaine-induced vasospasm resulting in muscle ischemia, excessive energy demands on the sacrolima muscles, and the toxic effects on the myocytes as well. And intravenous cocaine use is associated with a higher incidence of rhabdomyolysis. Some of the pearls to take away from here, there are many, and as we did discuss earlier, unfortunately 30 minutes does not give us due time to become complete toxicologist experts in the field. But with that being said, that we have hopefully established early recognition and identification of toxidromes and presenting clinical features. So you're able to identify them, working in parallel with your diagnostic and therapeutic interventions in narrowing down that toxidrome diagnosis. Keeping in mind that toxidromes can often overlap. It's on more of the lower incidence that generally they are a sole intoxication alone and use your resources to help you identify them. If you do have the ability to have or reach out to a toxicology team through your institution, your pharmacist, there is a National Poison Information Service Control Center, X-TRIP, which I mentioned earlier, the CDC, the CDC is a national poison information service control center. The CDC, as well as NIH, all have wonderful resources in terms of toxidromes and or the ability to identify and take care of them. Thank you for your time. I appreciate it and we will shortly take questions.

toxidromes

illicit drug abuse

ICU

drug overdose

metabolic profiles

supportive care

opioids

antidotes