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Melanie Cole (Host):  Welcome. This is Expert Insights with the Carle Foundation Hospital. I’m Melanie Cole and today, we’re discussing toxidromes. Joining me is Dr. Omobolawa Kukoyi. She’s an Emergency Medicine Physician with the Carle Foundation Hospital. Dr. Kukoyi, what is a toxidrome for healthcare providers that don’t necessarily know what this is please tell us what that is.

Omobolawa Kukoyi, MD, MPH (Guest):  Hi Melanie. First off thank you so much for having me. And so a toxidrome is a constellation of symptoms which suggest toxic levels or overdose of a certain group of drugs or chemicals, so pretty much you look at a patient, the exudates and set of symptoms and then that can fit into part of a puzzle. And there are several of them but there are four major ones we will discuss today. And the first one is the anticholinergic toxidrome, the second is the sympathomimetic toxidrome, the third is the opiate/sedatives and then the fourth is the cholinergic toxidrome.

Host:  Well thank you for answering that because I was going to ask you about the major toxidromes so thank you for that answer. What are some of the toxic effects that are caused by these that you’ve seen in your practice?

Dr. Kukoyi:  Absolutely. So, there’s a – I would like to classify this but before I go into the classifications, I want to give just a quick background. And so we have a pathway in our body called the autonomic nervous system. It pretty much controls or involuntary responses such as breathing. Now there are two main pathways. The first one is the very popular one that is our fight or flight otherwise known as a sympathetic response so things like speeding up your heartrate, sweating, expanding your lungs, the sympathetic pathway controls that and a neurotransmitter enzyme in that pathway is called norepinephrine.

The second response is the opposite. It slows things down. It’s called the parasympathetic response and the main neurotransmitter is called acetylcholine. So, these toxidromes that we are going to be discussing, they affect each of those pathways.

Host:  Well thank you. Tell us how. What are some of those pathways? How are they affected?

Dr. Kukoyi:  So, we can start with again grouping them. We can start with the cholinergic toxidrome pathway. And so, we mentioned that the parasympathetic was the opposite of the sympathetic and it slows things down, meaning your heartrate is decreased, your eyes or no longer dilated and guess what, antihistamines as a great example of drugs that can cause this potentially toxic levels. So, Benadryl, cough syrups, Nyquil, Dayquil, especially now during the COVID pandemic where we all hunkered down treating our systems at home; it is important to have an idea and recognize toxic levels. And so what these drugs do is that they block our parasympathetic response, meaning they block the slowing down and there was an aid in the medical school which is “hot as a hare”, “red as a beet”, “dry as a bone”, “blind as a bat,” “mad as a hatter”. So, pretty much people have fevers, you are flushed. You have dry skin, your eyes are really dilated, you are agitated. Again, remember that these antihistamines or those drugs they are blocking the parasympathetic response. And so which means that basically your body’s in a metabolic overdrive. People can have seizures leading to these, they can have kidney damage, liver damage and so the most important thing is early recognition and treatment is mostly supportive. Sometimes we have antidotes, but we use those for very severe cases. And so this is an example of an anticholinergic toxidrome meaning they block the parasympathetic response of the body.

Host:  Wow this is really a fascinating topic. So, as you are telling us how you narrow the differential diagnosis and how you use these historical clues and physical exam to reveal that toxidrome; tell us a little bit about a diagnostic tool, fundamental to effective medical response and to the degree Doctor to which that toxic symptoms present themselves. Does that depend on the route of exposure, the dose, what you know about the patient? Tell us a little bit about how you are identifying these.

Dr. Kukoyi:  So, it’s actually a combination of all of it. I cannot overemphasize the utility of trying to obtain collateral information from family or friends or even from EMS that picked up the patient at the scene. Because a lot of times, patients are altered or obtunded can’t really give you a good history and so you want to ask family, are they taking any medications, prescribed or nonprescribed, you want to also look at the age demographic of the patient. So, for example in an elderly patient, there are multiple medications and we call that polypharmacy and so it’s an easier time, you have like an easier way to overdose on those meds. You also kind of look at the patient. In emergency medicine, usually the first thing is when you come into the room what do you see and so you do a very thorough physical exam as safely as you can so are the pupils dilated? Is this person agitated? Are they sweating? Are they not sweating? What is the color of the skin? What is their temperature? And so all of these are pieces of a puzzle the hopefully can come together for you.

Host:  Well that’s really important for providers to hear. I mean it certainly is. So, let’s talk about when we’re taking that history, please describe for us some of the common prescribed medications that can cause some of these symptoms. Are we also looking at meds for diabetes, heart disease, common medical conditions and while you are answering that, some of the over-the-counter medications or now nonprescribed drugs even legalized marijuana, or illegal drugs that can cause some of these symptoms and in addition, Doctor, what about potential causes such as exposure, farming, since there are a lot of farmers in the area. Can you please cover the medications, the things that you are looking for when you take that history?

Dr. Kukoyi:  Absolutely. And a point I want to emphasize before going into this is, we don’t have to necessarily memorize all those drugs. The most important thing is recognizing the pattern. A lot of emergency medicine and medicine in general is pattern recognition. And so this is a great time to break down the toxidromes into the four pathways we talked about. I already mentioned briefly the anticholinergic toxidrome which we classified Benadryl, antihistamines underneath. But we have some prescribed medications that can fall in that category as well. So, you have pscyh meds, meds for depression, meds for anxiety and even antiseizure meds that can cause this so that’s why it’s very important to take a thorough history of each patient.

The second type of toxidrome is called the sympathetic toxidrome and remember that’s the pathway that promotes our fight or flight response. So, you have similar symptoms as this anticholinergic toxidrome in that your heart is racing, your lungs are expanded, your eyes are dilated but because this is a different neurotransmitter, you are constricting blood flow to the skin, you are actually sweating and so going back to my description of when you go into remote DUC, one of the distinguishing factors between the two is that in the sympathetic toxidrome patient, they are profusely sweating and some of the nonprescribed drugs in this category are coffee, yes coffee because coffee drives off the sympathetic system.

Obviously too much of a good thing becomes a bad thing. And so we have other drugs like amphetamines that are prescribed legitimately for ADHD issues but then you also have street drugs such as cocaine and meth that can ramp up this system. And in the setting of legalized marijuana, sometimes these are laced with like other street drugs such as meth, ecstasy and NMDA. So, it’s really important in asking patients that even when you use legalized marijuana, do you know where you bought this from, is there any possibility this could be laced? And the treatment is mostly supportive again similar to the anticholinergic toxidrome, it’s a metabolic overdrive. People are high risk of seizures, decompensation, so you want to control that fever, you want to control that heartrate. You want to sedate the patient just to help them help their body recover.

And so the third class of toxidromes is the opiates or sedatives. And so opiates actually bind to a different receptors than the autonomic nervous system. And so overdose can lead to respiratory depression such as people losing their respiratory drive, they have low body temperatures, go hypothermia. They have pinpoint pupils. And this is very important because this can quickly lead to death. In the light of this opioid crisis, we have all heard about the drug called naloxone or Narcan which is a lifesaving drug and it helps to reverse the effect of those opiates and especially in the elderly population like I mentioned polypharmacy is a big issue because they usually have comorbidities on multiple drugs. So, looking at grandma’s list is grandma on Norco, is she on Percocet, is she on Vicodin? Could she maybe have taken that Vicodin with a Benadryl. So, those are things to think about.

In terms of the sedative toxidrome, benzodiazepines so Xanax, Ativan, things that are prescribed for anxiety issues can also cause sedative symptoms. Again, the treatment is supportive. Controlling their airway, do they need to be supported by the ventilator while their body is going through this? Do you need to give them IV fluids. A lot of this is just really supportive care.

And then you also mentioned chemical exposure to pesticides. That brings me to the last one on the list, SLUDGE toxidrome that I’m talking about. It’s called the cholinergic toxidrome which pretty much means that you have an overdrive of the slowing system and so I mentioned that acetylcholine is the main neurotransmitter of your slow system which is the parasympathetic system and pretty much the drugs prevent the breakdown of that enzyme and so we just have excessive secretions everywhere and an aid we learned in medical school is called SLUDGE so that’s salivation, lacrimation, that’s tearing from the eyes, urination, diarrhea, GI distress and emesis which is vomiting. So, pretty much you are leaking everywhere. You are salivating, your are tearing up, you are having diarrhea. It’s a very unpleasant toxidrome and so especially when you have farmers come in and you have this constellation of symptoms, it’s important to recognize that it might be due to pesticide exposure for example. Again, a lot of this is supportive treatment. So, fluids for possible dehydration, just kind of supporting their overall hemodynamics. I hope this makes sense.

Host:  I totally does. Absolutely so interesting. So, Dr. Kukoyi, specifically for example during say a mass exposure, can this recognition that you’ve given us such really great education on today; provide a triage tool for identifying exhibiting toxic effects and also provide a common language as it were so that emergency responders from the scene through to the hospital ED can clearly communicate a clinical message?

Dr. Kukoyi:  So, with the EMS providers, they have a very limited time with the patient. And again, it’s recognizing patterns so it may actually take a while to figure out if this is like a toxic exposure. But let’s take opiate exposure for an example. The common things are pinpoint pupils, or called a myosis, sedation, and so those are very pretty easy toxidromes to recognize and our EMS colleagues have actually been trained to administer the antidote naloxone in the field with good success. In terms of the other less common ones so for example, our anticholinergic or our sympathomimetics which is the like metabolic overdrive toxidromes, usually they’ll say patients are agitated, patients are hyperthermic meaning they have a high fever, so a lot of it is supportive care.

So, coming to the ED they can keep the fever down, they can kind of keep some sedative medication and so it’s we in the ED that after getting history and collateral information that can sometimes fit those puzzles together. But even if you can recognize a pathological  at that moment in time, it’s important to recognize that your first step is supportive care. And so if their airway is depressed, I need to control that airway, I need to give them oxygen support. If their blood pressure is low, because they are having profuse diarrhea everywhere you need to give them IV fluids and so the most important thing is not being able to identify the toxin, eventually you probably will when you have more collateral information; but the very first step is recognizing that this patient might be in danger and I need to control their symptoms.

And some of the intents of a mass exposure so nerve gases is like sarin, they actually – they cause the cholinergic toxidrome which is the profuse secretions everywhere and so when you have for example like a group of people coming from the same house or coming from the same community with the same symptoms; then your index of suspicion should be much higher.

Host:  Wow. Great education for responders and other healthcare providers. Before we wrap up, what’s important to recognize as far as disposition of patients? Tell us why you consider hospitalization and monitoring versus discharging home and give us your best advice. Wrap it up for us if you would.

Dr. Kukoyi:  Yeah absolutely. So, unfortunately, by the time patients are sick enough to come to the emergency room from this toxidrome they probably will need to be admitted. So, people with less severe symptoms so if you just having a cholinergic so diarrhea, vomiting, I can pretty much hydrate you, give you some medications for the nausea and keep you on the medical floor but people that are coming in with the anticholinergic and the sympathomimetic which has the overdrives may likely need to go to the ICU because your body just cannot keep up with that metabolic demand.

A lot of times, when we need to give you sedative medications which can cause the respiratory depressions that we talked about; and so sometimes that may necessitate us putting you on a ventilator which can only be managed in the ICU. So, I would say severe cases will have to go to the ICU. Patients that I will discharge home again by the time they make it to the ED, probably not. But if some people come and things like amitriptyline, gabapentin, they have like little dizziness, dryness, we can kind of caution on discontinuation of those drugs or reducing the dosage and give them like strict return precautions, but disposition will depend on the severity.

And so wrapping things up, it’s history, history, history. If there is family, ask EMS did you see any drugs on the screen and every time a patient comes to you in clinic or in the ED and you are reviewing their history, make sure that every time you are asking is your medication list up to date. Because if push comes to shove, that may be all we are relying on.

Host:  Great information. So, informative. Dr. Kukoyi, thank you so much for joining us. And that concludes this episode of Expert Insights with the Carle Foundation Hospital. For a listing of Carle providers and to view Carle sponsored educational activities please visit our website at www.carleconnect.com for more information and to get connected with one of our providers. We hope the information gained will be applicable to your work and life. This is Melanie Cole.