Salicylate Toxicity Explained Clearly | Acid Base Disorders, Intubation Pitfalls & ICU Management

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[00:00:00]Hey everybody, and welcome back to another [clears throat] episode here of WhiteBoard Medicine. We appreciate you checking it out. Hope everybody's having a good day today.

[00:00:08]Today's topic is going to be one central to emergency critical care medicine. And that is salicylate toxicity. This is toxicity that comes from overconsumption of salicylates. Um aspirin being probably the most common one, but there's a number of different products that have salicylates in them.

[00:00:28]And it creates a really interesting and then unfortunately quite significant way that can make people really sick pathophysiology that results from it. So, we're going to dive into all things salicylate toxicity today. We'll talk about what it is, symptoms, signs, pathophysiology, diagnosis, management, you know, unique circumstances. And then at the end of the episode, we'll have practice questions and kind of some high-yield board review as well for those who, you know, are watching the episode to get a grasp on um salicylate toxicity from board view standpoint. But there will certainly be lots of bedside nuggets, too. Um so, no further ado, let's dive into salicylate toxicity. So, why does this matter? Why are we talking about it today? If you're familiar with the channel, you know that we've talked about beta-blocker toxicity and calcium channel blocker toxicity and acetaminophen and sympathomimetics and a whole bunch of other stuff. If you're interested in any of those episodes, um just search WhiteBoard Medicine um followed by, you know, whichever one of those episodes you're interested in. So, we've talked about a bunch of different toxidromes, but why salicylate? Why now?

[00:01:30]Well, salicylate poisoning is one of the kind of classic toxicologic emergencies seen in the emergency department, certainly seen in the ICU. And these patients can deteriorate quite rapidly even when they might have some reassuring vital signs and laboratory values initially. And that is critical, right? You don't want to be falsely reassured based on the initial presentation cuz these patients can decompensate quite quickly. Severe toxicity can cause mixed acid base derangements. This is classic salicylate toxicity stuff that we'll talk more about. Neurotoxicity, pulmonary edema, hypo- hyperthermia, and cardiovascular collapse. Right, all these things we're going to dive into more as this episode progresses, but all these are really severe. Many of them can end up being fatal if they're not appropriately managed. And we should say, if anyone is interested in this study guide, this PDF that we are going through in this episode, all of them are available on our Um if you don't know our Patreon page, we have been working really hard to build an emergency critical care medicine Patreon community, and we've had a ton of great feedback from people.

[00:02:34]The community is growing like mad, which we're so excited for. And we have every PDF or study guide from all of our episodes. We also have mini courses. We have ad-free videos, clinical reviews, practice questions, medical education posts. It's, you know, probably one of the larger uh emergency critical care educational collections out to there and available um with kind of full comprehensive emergency critical care and ICU curriculum stuff. So, definitely check that out, linked in the episode description as well as the pinned comment if you're watching this on YouTube. Okay, enough of that.

[00:03:03]Salicylate toxicity, the most dangerous mistake is failure to recognize, specially worsening CNS salicylate penetration. This is a cru- key concept.

[00:03:15]And if you're unfamiliar with what we're referring to, that means that we have plenty to learn in this episode. So, patients can appear deceptively stable until they suddenly decompensate.

[00:03:24]Let's start by talking about common sources of salicylates. Where can patients either intentionally or unintentionally consume too much salicylate? Well, the first and the main one, as we mentioned, is aspirin. Um this is the most common um salicylate that is consumed. Um it's the most common cause of salicylate toxicity is overconsumption of aspirin, again, whether intentional or unintentional.

[00:03:48]Another one, and these ones are uh are um uh sometimes formulations that people and patients don't necessarily know contain salicylates. One is oil of wintergreen. This is very concentrated salicylate. You have to be incredibly careful with this. One teaspoon of oil of wintergreen has around 7 g of salicylate. This can be lethal. This can be deadly. You can die from consuming this. Um so this is a huge one to look out for. And then other sources you might not think about are bismuth subsalicylate. Um not that brand names are what we put forward here. We always try to stick with generics, but Pepto-Bismol would have some bismuth in it. Topical salicylates, you do absorb portions of topical salicylates, some herbal products, combination of cold medications. And this is a really important one, right?

[00:04:37]For these unintentional salicylate toxicities, it usually involves polypharmacy. You know, maybe a patient took aspirin and knew that aspirin had salicylate, but maybe they also took Pepto, didn't realize that had salicylates, they used some topical salicylates as well, didn't realize that, and then they took some cold medication for whatever reason, right?

[00:04:55]This might be a concoction that could cause toxicity, but a patient may not have realized that all these formulations had salicylates in them. So it's a good rule in general, right?

[00:05:04]Polypharmacy and unintentional consumption of compound formularies that contain uh salicylates in them is a cause of salicylate toxicity that can sometimes get fly under the radar cuz patients don't come in and say, you know, I took too much aspirin. Um they come in with symptoms and don't realize those symptoms are secondary to a combination of medications that they were on.

[00:05:27]So toxic dose overview, um we want to go through kind of approximate um milligrams per kilogram of salicylates that can cause toxicity.

[00:05:37]Know though, just like everything in this episode and on our channel, none of this is intended to be acted upon as medical advice. This is all educational.

[00:05:44]Um this is not a hard and fast rule, but it may be from an educational standpoint will give a baseline. So, if you have less than 150 mg per kilogram of salicylates, you can get minimum toxicity, but usually minimal. Anything above that, right? 150 to 300 mg per kilogram can cause mild to moderate toxicity. 300 mg per kilogram to 500, severe toxicity. And more than 500 mg per kilogram this can be potentially be lethal. So, if we think of it from that standpoint, um it's really important that we keep track of the dosing of salicylates that's being consumed. And when a patient comes in with potential salicylate toxicity, you can ask them.

[00:06:20]Sometimes they know. Certainly, you know, trust but verify. Um so, you shouldn't uh put all your um money in that single bucket based on what the patient said. But if the patient said, you know, I took Let's just try to make it easy. Aspirins that are 300 mg and they say that I took 10 of these. That's 3,000 mg, right? And that's 3 g of aspirin. Now, if the patient only weighs let's say 50 kilos, um 50 kg. So, 50 um divided 3,000 divided by 50. We should really stop doing math on the channel. But this would be a minimal toxicity, probably. Now, if they said I took 100 300 mg aspirin, now we're talking about 30,000 mg or 30 g.

[00:07:10]Um again, we won't try to do math again, but this could potentially be a significant toxicity. So, ask the patient. Sometimes they know, but sometimes they don't. You should never fully trust that reporting, but it can sometimes put things in the ballpark for you. Um do note to know that the clinical status of the patient matters a lot more than the serum level. And we'll get into serum levels a little more as we progress. Um but just cuz a level in the blood is um a certain level does not necessarily mean the patient is having severe or mild toxicity. Clinical status, the patient signs and symptoms are much more important when talking about severity of ingestion.

[00:07:46]Pathophysiology, this is where salicylate toxicity gets really interesting, at least if you're a big nerd like we are. So, salicylate toxicity produces a unique combination of pathophysiologic derangements, right?

[00:07:59]It affects the respiratory system, metabolic system, neurologic system, thermoregulatory system, all can become deranged. And understanding this physiology is critical because it derives a lot of our management decisions. It certainly helps explain a lot of the symptoms and signs you might be seeing as well when you're evaluating these patients.

[00:08:19]Um >> [snorts] >> So, the body when you have salicylate toxicity compensates and these compensatory mechanisms can sometimes be life-preserving. So, understanding the compensatory mechanisms are important, too, and that's what we're going to dive into.

[00:08:32]So, the first thing we wanted to talk about, we're going to take a swig of water here, keep the throat fresh.

[00:08:37]>> [snorts] >> Apologies.

[00:08:39]Um The first thing we want to talk about was direct respiratory center stimulation.

[00:08:46]And what we're talking about here is salicylate actually directly stimulate the medullary respiratory center. And this causes the initial tachypnea, hyperventilation, and a respiratory alkalosis because as your respiratory rate increases, your amount of dissolved CO2 in your blood, your PCO2 decreases, and that leads to a respiratory alkalosis.

[00:09:11]And this is one of the first parts of the complex acid-base disturbances that can occur, a respiratory alkalosis because that salicylate is directly stimulating your medullary respiratory center.

[00:09:22]Um this often leads to the earliest physiologic abnormality. Patients may present with deep rapid breathing, low carbon dioxide levels, and an elevated pH, right? Alkalosis.

[00:09:32]Um and this hyperventilation is often actually protective, not pathologic. And why it is protective?

[00:09:39]And we're going to get way more into this. So, if this doesn't register right away, there will be ample opportunity for us to talk more about it. But, the respiratory alkalosis actually helps to keep salicylates ionized. If they're ionized, they have less CNS penetration, and it can delay worsening toxicity. One of the therapeutic measures we're going to talk about is actually alkalinizing the blood and urine, right? Giving bicarbonate. So, again, we're skipping ahead a little bit, but that respiratory alkalosis um actually can help protect the patient from some of the really severe sequelae of salicylate toxicity.

[00:10:13]Um so, respiratory alkalosis, symptom number one.

[00:10:17]Uh sorry, pathophysiologic principle number one. Pathophysiologic principle number two, uncoupling of oxidative phosphorylation.

[00:10:25]It sounds as bad as it is. This is one of the most important mechanisms in severe toxicity. So, normally, a patient, a person, the mitochondrial electron transport chain generates ATP.

[00:10:39]This is an efficient process. It's kind of the highest energy yield process. Um this is how we all survive, how we all make ATP. This is critically important.

[00:10:47]People cannot survive for prolonged periods of time without functioning mitochondria electron electron transport chains generating ATP. Salicylates though disrupt this process, and they do it by uncoupling oxidative phosphorylation.

[00:11:03]So, essentially, the mitochondria's electron transport chains need to have oxidative phosphorylation to produce ATP. So, salicylates uncouple this process and make it so we can't effectively have oxidative phosphorylation. As a result of that, ATP production decreases, right? ATP is energy. So, without ATP, the body starts to not be able to function adequately.

[00:11:29]You also start to generate a lot of heat. The body gets very warm, and you start to consume huge amounts of oxygen because you're not able to utilize that effectively. This leads to hyperthermia, increased metabolic demand, lactic acidosis. This lactic acidosis is because you have to start doing anaerobic metabolism uh because again, you cannot effectively use your electron transport chains. So, anaerobic metabolism causes lactic acidosis and cellular energy failure. Your ATP levels are going to go way, way down, and this is can be fatal if it gets bad enough, right? So, uncoupling oxidative phosphorylation, patients essentially enter a hypermetabolic state.

[00:12:13]Pathophysiologic principle number three.

[00:12:16]Um and this is connected to the previous one. You start to get increased anaerobic metabolism and organic acid production. So, as ATP generation becomes inefficient, right? Because we have uncoupled that electron transport chain in our mitochondria, so we're not able to effectively create ATP. Cells shift towards anaerobic metabolism, as we mentioned. That anaerobic metabolism starts to generate lactate. You also start to generate keto acids because without effective ATP production, you start to break down more fatty acids into ketones, and those ketones are acidic. So, you get keto acids and other organic acids. This then drives the next part of the acid-base disturbance, which is an elevated anion gap metabolic acidosis.

[00:13:07]Right? So, metabolic acidosis from an elevated anion gap. And that anion gap is elevated because of lactate, because of ketones, and other organic acids. So, you get Now, you have a respiratory alkalosis, okay? With >> [snorts] >> an anion gap metabolic acidosis.

[00:13:28]This is a classic classic board question. It does happen in real life, too. It's important to know. Respiratory alkalosis with metabolic acidosis, an anion gap metabolic acidosis.

[00:13:39]So, do note though that this metabolic acidosis develops later than the respiratory alkalosis in most adults, although children may present predominantly acidotic earlier in their course.

[00:13:50]All right.

[00:13:51]Pathophysiologic principle number four.

[00:13:54]You start to get a lot of glucose dysregulation.

[00:13:58]So, the salicylates, as we said, increase metabolic demand. That increased metabolic demand is secondary to a lot of that uncoupling. That then increases [snorts] glucose utilization. Increased glucose utilization can produce hypoglycemia cuz you start to run out of glucose.

[00:14:15]This is really important, right?

[00:14:17]Hypoglycemia [clears throat] is one of those possible symptoms of salicylate toxicity.

[00:14:22]The next sentence I'm going to say though is really really interesting in an unfortunate way.

[00:14:29]Cuz the other thing that can happen is even when you have normal serum glucose, you do a point of care glucose check or you get a glucose back on your basic metabolic panel and it is normal, you still actually can have hypoglycemia in your CNS, CNS glucose depletion.

[00:14:46]And we're going to get more into this.

[00:14:49]But what can happen is the salicylates can penetrate the CNS, okay? And when they're in the CNS, they can cause separate dysregulatory uh malfunctions in the CNS that can lead to hypoglycemia in the CNS despite a normal serum glucose level. So, patients may have, you ready for it?

[00:15:05]Neuroglycopenic symptoms even when the fingerstick glucose appears normal. I'm going to say it again. Patients may have neuroglycopenic symptoms even when the fingerstick glucose appears normal.

[00:15:19]This is why in some patients, if you are symptomatic, even if your glucoses are normal, you might still start a dextrose uh solution to try to drive up that CNS glucose.

[00:15:33]Interesting. Gosh, toxidromes are wild.

[00:15:36]Okay, um pathophysiologic principle number five. Sorry, we are such pathophysiology nerds, but in our minds at least, understanding the pathophysiology really helps the rest of things settle in, right? We're going to be talking about management, signs and symptoms, uh severity, all that kind of stuff, and understanding the pathophysiology will help us understand why all those symptoms are arising and how to manage them. So, principle number five, CNS penetration and acidemia. Um hopefully some of this is kind of falling into place cuz there's a lot of overlap. We've mentioned these things.

[00:16:08]So, this is the most dangerous physiologic turning point in salicylate toxicity. To understand this, we have to understand ionized form and non-ionized form. So, salicylates exist in an ionized form, which means it has a charge, right? Ionized means it has a charge. And a non-ionized form, it's neutral. There's no charge. The non-ionized form of salicylates can cross the blood-brain barrier much more easily, right? So, you have a brain. We can't draw to save our lives, but this is going to be a little brain squigglies. But, this brain is surrounded by a blood-brain barrier, okay?

[00:16:44]And this blood-brain barrier only lets in certain things.

[00:16:48]One of the things that it does let in though is the non-ionized, the neutral salicylate molecule. And this neutral salicylate molecule then can get into the brain and wreak havoc in there, all right?

[00:17:03]Now, >> [snorts] >> acidemia, right? We said these patients have a respiratory alkalosis early on, and then they have an anion gap metabolic acidosis. Acidemia shifts salicylates towards the non-ionized state. So, if this acidemia gets bad, ionized salicylates, right? They're ionized, they have a charge, so they don't readily cross the blood-brain barrier, they start to shift into the non-ionized form of salicylates, and the non-ionized forms of salicylates, as we said, can cross the blood-brain barrier and cause the terrible CNS effects you can see.

[00:17:41]So, as serum pH falls, CNS salicylate penetration rapidly increases, and the neurotoxicity worsens, which is really critical. This can lead to agitation, delirium, cerebral edema or swelling of the brain, seizures, coma, right? All these things can end up being fatal.

[00:18:03]Even small drops in the pH can dramatically worsen toxicity, which we need to remember this cuz it's going to play into some of our management approaches, which aren't as maybe typical for um patients who um are coming with different other complaints.

[00:18:18]This is why acidemia is dangerous. This is why hyperventilation, that respiratory alkalosis, um is protective. And this is why, and we're going to talk way more about it, but intubating these patients can be catastrophic if ventilation is inadequate, right? Intubating these patients can lead to death because we need these patients to maintain their respiratory drive to try to hyperventilate, increase their minute ventilation, and drive an alkalosis cuz any worsening acidemia is going to increase salicylate CNS penetration and cause worsening CNS effects.

[00:18:53]>> [snorts] >> All right, onto the sixth pathophysiologic principle, and this is the last one. So, if you've made it down here, you're a pathophysiology nerd like the rest of us. Let us know um if you've uh decided to dip out or skip ahead, this is the last one, so um skip a little bit further, I suppose. Okay.

[00:19:11]Pathophysiologic principle number six is pulmonary edema. This isn't your run-of-the-mill pulmonary edema. Severe salicylate toxicity can actually cause non-cardiogenic pulmonary edema. Right, so cardiogenic pulmonary edema is you're fluid overloaded, you have heart failure, and that causes fluid to back up in the lungs and cause pulmonary edema. Non-cardiogenic pulmonary edema means you don't have heart failure, you're not fluid overloaded, there's something else causing fluid in the lungs. And the mechanism is poorly understood, but people think it's from increased capillary permeability in the lungs, maybe direct lung injury, maybe increased metabolic stress. So, it's unclear what's totally driving this, but you start to get pulmonary edema that is not from the heart. And this may cause hypoxemia, infiltrates on chest x-ray, respiratory distress, and being unable to adequately ventilate can worsen acidemia and start the vicious cycle of toxicity, right? Increasing that CNS penetration because you have worsening acidemia, leading the salicylate to go from ionized to non-ionized, which then can more readily pass the blood-brain barrier and get into the brain.

[00:20:19]>> [snorts] >> All right, good work. On to a brief discussion, um emphasis on brief, on the classic acid-base pattern because this is something commonly tested, and we do see it in patients in the clinical arena, which makes it even more important. Some things are tested, but you don't really see them, some things you see them and aren't tested. This is one of those things that uh check both boxes, which is atypical and critical.

[00:20:43]>> [snorts] >> All right. So, adults classically develop and you all, if you've been paying attention, hopefully can fill this in.

[00:20:52]Adults classically develop a respiratory alkalosis. Remember, this often happens first, it's cuz that salicylate affects the medullary centers in the brain, which increases our respiratory drive.

[00:21:02]This is followed by an anion gap metabolic acidosis. This is usually second or later, And this is because you get the uncoupling of oxidative phosphorylation. This increases lactic acid. This increases ketones like beta hydroxybutyrate. And all of these things contribute to an anion gap metabolic acidosis.

[00:21:24]All right? Children may present with a metabolic acidosis earlier, but just note that a near normal pH does not exclude severe toxicity.

[00:21:34]Because a near normal pH might be a combination of your respiratory alkalosis plus your metabolic acidosis.

[00:21:42]Your anion gap metabolic acidosis. And this may lead to about normal pH, but you still may have severe toxicity. So, don't let that fool you. Again, this is commonly tested on, so put that in your brain hole. All right. [snorts] Clinical features of salicylate toxicity. A lot of these things hopefully will be you know, um, explanatory in the sense that we understand the pathophysiology and many of these symptoms are related to that. So, early findings of salicylate toxicity. Nausea, vomiting, tinnitus, which is ringing in the ears, tachypnea, right? Because you have a respiratory alkalosis cuz that salicylate stimulated your medullary centers and increased your respiratory drive. Diaphoresis cuz you get a little hypermetabolic.

[00:22:21]You have dysregulation in your thermoregulatory centers. Um, and it causes you to be hot. Fever, same thing.

[00:22:27]Diaphoresis and fevers. And dizziness cuz you start to get some early CNS penetration. So, you can start to see how some of these symptoms line up with the pathophysiology we talked about.

[00:22:37]This then can progress to moderate toxicity. And this is where things start to get bad. Agitation, confusion, right?

[00:22:45]These are because of increasing CNS penetration. Right? You might get more acidemic, which will allow more of that ionized to non-ionized salicylate to get into the brain. Start to get tachycardic, right? This tachycardia is primarily driven by the fact that you're no longer able to oxidatively phosphorylate. Um, and you, uh, are not making as much energy, so your heart goes into overdrive.

[00:23:06]Hyperventilation, you still have that respiratory alkalosis, and then ketosis, right? Because again, you've uncoupled oxidative phosphorylation, your body's starving for energy, so it starts to perform ketosis by breaking down fatty acids. So, right? Pathophys, it all comes back to pathophys.

[00:23:24]Okay. Um, severe toxicity is where things get deadly. And hopefully, you've diagnosed and intervened here, but you start to get altered mental status, seizures, coma.

[00:23:34]Right, this is severe CNS toxicity.

[00:23:39]You get that non-cardiogenic pulmonary edema from pulmonary capillary leakage.

[00:23:44]Again, hyperthermia, your thermoregulatory centers are all deranged. You got a refractory acidosis from that uncoupled oxidative phosphorylation increasing lactic acidosis and ketosis. And it can eventually lead to cardiovascular collapse, right? And this can certainly obviously lead to death. So, this is a potentially fatal ingestion, very complex and potentially fatal. Hard to diagnose, too, without someone telling you they took a bunch of salicylates.

[00:24:12]So, good transition, important diagnostic pearls. Tachypnea here is protective, so note that. Patient might be tachypnic early. This is to maintain an alkalemia, cuz this alkalemia will change the ionized version.

[00:24:27]Oh.

[00:24:28]This alkalemia will change the non- ionized version of the salicylate to the ionized version, and the ionized version has a charge on it, so it does not cross the blood-brain barrier as easily.

[00:24:44]Pulse oximetry can be misleading in these patients, right? Oxygen saturation does not exclude severe toxicity, so don't let that make you feel falsely reassured.

[00:24:54]And then, do note that salicylate levels can rise late.

[00:25:00]So some aspirin is enteric-coated. You can get a bezoar. This is where you take so many pills right of the esophagus, goes into a curve, you got your tummy, and that tummy dumps out into your small intestine. Um if you take a bunch of pills, right? Sometimes they actually stick together and they form this bezoar that's all clumped together and sticky, and this takes more time to break down and get um metabolized. So bezoar formation can cause salicylate levels to rise late. Delayed gastric emptying, right? Some people have gastroparesis from things like diabetes or just delayed gastric emptying in general. All that can lead to a salicylates rising late. So always obtain serial salicylate levels. Don't assume the first one or two is kind of the peak that you're going to come across.

[00:25:44]All right, initial evaluation of these patients um we're not going to spend too much time on here. Again, none of this is intended to be construed as medical advice. It's all just educational, but you can see some generic labs. A lot of these labs are kind of generic toxidrome labs. You want a basic metabolic panel, liver function tests, arterial blood gas or venous blood gas, serum salicylate, lactate, glucose, ketones, CBC, coags, Tylenol level because they might have mixed polypharmacy, pregnancy test if applicable. Um and again, a lot of this hopefully you're starting to think about, right? The BMP, and CMP, the blood gas cuz you would initially have that respiratory alkalosis and then anion gap metabolic acidosis later. Serum salicylate levels, but do remember um that they might not peak quickly, especially if you have an enteric-coated aspirin ingestion or bezoar formation um or polypharmacy.

[00:26:29]Lactic acid because you get uncoupling of oxidative phosphorylation, that lactate goes up. Glucose um because you can get hypoglycemia, and you need to consider CNS hypoglycemia, that neuroglyco uh hypoglycemia. We actually forgot the cool name, but we are so interested in the cool name, we are going to scroll up uh and say it again so that we can all say it together. Oh boy, it was higher up than we thought.

[00:26:53]Bear with us.

[00:26:55]Um >> [snorts] >> or we're going to have to punt and then you can tell us in the comments what we forgot. All right, fine. We'll punt. Let us know in the comments the cool name for a hypoglycemia in the CNS. Something like neuroglycopenia or something. Okay.

[00:27:09]Um ketones because you're no longer using oxidative phosphorylation to create energy, so you start to break down more fatty acids, which form then ketones. CBC coags classic um toxidrome uh labs and then a Tylenol level because polypharmacy is quite common. EKG, chest x-ray, remember there's a non-cardiogenic pulmonary edema that can develop. Um and then remember serum levels support diagnosis but do not determine severity alone. A patient with severe symptoms, acidemia, or CNS findings may be critical critically ill despite moderate serum levels. Um some people say to try them every 2 hours, although your poison center We should have said this even earlier on. Your poison center is your best friend. Use them. Call them. Talk to them. They are so helpful. All right.

[00:27:53]Um if you live in the states, you can If you don't know the number, you can literally just Google it. Um say poison center number near me or poison center Illinois or poison center Michigan or poison center uh California or wherever you live. Um so use them.

[00:28:09]All right, let's talk about a little um therapeutic approaches. The first thing to mention is activated charcoal. This is a tough one, right? You can consider it if the presentation is within several hours, their airway's protected, the patient's cooperative. But just note, right? Call poison control or talk about this with your local toxicologist. The decision to activate a charcoal is complex, but it can work in salicylate toxicity, so it is an option on the table. The cornerstone of therapy though, what is going to save lives, is alkalinization, which hopefully you're thinking about why based on the pathophysiology. So why it works, remember alkalemia reduces CNS penetration cuz Cuz go from ionized to non-ionized.

[00:28:49]>> [snorts] >> Um we are going to constantly say that wrong.

[00:28:52]Revamp, you go from non-ionized to ionized because ionized has a charge and has less CNS penetration.

[00:29:02]It also helps you increase urinary excretion of the salicylates. This is how you get rid of them. This is really important. So, this is the key therapy for most symptomatic patients, right?

[00:29:12]Alkalinize them. Target a serum pH of 7.45 to 7.55, a urine pH of greater than 7.5, and use bicarbonate to do that. Do [snorts] note that these patients have to be you um normokalemic.

[00:29:28]Their potassium has to be normal um because potassium is critical in urinary alkalinization. Hypokalemia will prevent you from being able to adequately alkalinize the urine. So, ensure potassium is within normal ranges and repleated as you need to um because without it, you might not be able to alkalinize that urine effectively.

[00:29:49]So, alkalinization is the key therapy here, right? Use bicarb and do it. Um fluids, patients are often volume depleted, right?

[00:29:59]Hyperventilation causes insensible losses. We don't have to think about that, but if we're panting away, we're losing um fluids in our breath every time we're panting. Fever, vomiting, all these things are going to cause hypovolemia. So, resuscitate these patients with fluids, but do remember some of them develop non-cardiogenic pulmonary edema. And although that's not a volume problem, um dry lungs are happy lungs, or so they tell us.

[00:30:22]Um so, uh you just want to be careful.

[00:30:24]You want to be thoughtful about that.

[00:30:25]Glucose management, we have mentioned this a couple times. We're going to keep hammering it home. CNS glucose depletion may occur despite normal serum glucoses.

[00:30:35]Give dextrose if they have neuro symptoms, altered mental status, neuro symptoms, or even a borderline serum glucose, right? So, give them D5 when in doubt. Probably just start them on a dextrose solution.

[00:30:47]Intubating these patients, oh goodness, this is a high-risk maneuver. Um so, intubation can kill these patients. This is one of the highest-risk airways in emergency critical care medicine because any apnea, any hypoventilation can rapidly worsen acidemia. And this rapidly worsening acidemia, even with a brief hypoventilation, can precipitate cardiac arrest, right? This makes us incredibly nervous. So, avoid intubation if at all possible.

[00:31:15]Try non-invasive if they can tolerate it. Give bicarbonate, fix their glucose, address their volume status, do everything you can to potentially reverse or improve them to avoid intubation. If you have no choice left, the patient is going to die without being intubated, this is a physiologically difficult airway.

[00:31:35]Be thoughtful, have a plan, and get ahead of this as best as you can, right?

[00:31:40]Bolus them bicarbonate as much as you can to drive that pH up before you induce them to intubate them. Prepare the ventilator in advance. Avoid apnea at all costs. Um if it's interesting to you, let us know. We can do a whole episode on kind of physiologically difficult airways. There's a lot there to think about, and this is probably not doing it any justice at all um because there's a lot of thought uh and steps you can take to try to um make this incredibly dangerous high-risk airway maybe a touch less dangerous, although certainly does not take the majority of the risk away.

[00:32:11]The other thing to note is once you put them on a ventilator, you really need to try to match or exceed their pre-intubation minute ventilation, right? Minute ventilation is respiratory rate times tidal volume.

[00:32:21]This is the cc's of air they were breathing per minute. Um and that is what their body needed to stay alkalinized. So, you need to try to match this or supersede it because if you don't, their respiratory alkalosis that is helping save their life is going to go away, and they're going to get more acidotic, and remember acidemia kills these patients. So, they may require higher respiratory rates, larger minute ventilations. If you do not paralyze the patient, you can trial pressure control rather than volume control cuz pressure control will let them take big tidal volumes in a way that volume control doesn't always let them. Now, you got to be careful with pressure control because the tidal volume is an uncontrolled variable. So, if they're breathing okay on pressure control and you step away and all of a sudden start breathing less, again, they could die. So, this is a very high-risk intubation. This ventilator is going to need a lot of close attention, um and the things here are apnea and hypoventilation kill these patients. So, you have to decrease apnea time, ensure you're alkalinizing them, and once they're on the vent, try to match their previous minute ventilation, which is hard thing to do, um but allow them to take high tidal volumes. This is not the patient you put on 6 cc's per kg tidal volume and hope for the best, right?

[00:33:31]That will be an assassination attempt.

[00:33:35]Okay.

[00:33:36]>> [snorts] >> Other management principles, hemodialysis. This is a definitive therapy for patients with severe salicylate toxicity. It removes the salicylates, corrects acid-based arrangements, corrects electrolytes, removes fluid as you need to. The common triggers here, um this is complex, so again, talk to your subspecialist, whether it's poison center toxicologist, but CNS symptoms like altered mental status, non-cardiogenic pulmonary edema uh that's severe, severe acidemia, renal failure, rising salicylate levels, clinical deterioration, refractory electrolyte derangements, severe hyperthermia, inability to effectively alkalinize. All these are possible indications, but pulling your subspecialist, this can be a complex kind of decisional tree, and one that can change over time, too, right? A decision to not do it um can change an hour later, and it might be a decision to do it, but hemodialysis is definitive therapy for these patients, um and it can save their lives, so don't drag your feet um if they need to be dialyzed, put in the dialysis catheter and get it done, right? Let's keep them alive. We can pull the dialysis catheter out later.

[00:34:36]All right, major pitfalls. We're close to the end. We'll get some pitfalls, some high yield board pearls, some final kind of clinical bedside pearls, and then practice questions. So, if you made it this far, finish it out, and you will maybe be the master of salicylate toxicity, or at least well on your way.

[00:34:50]All right, pitfall number one, intubating without matching their minute ventilation. The intubation procedure is high risk, but putting them on the ventilator even after that remains high risk. So, be very thoughtful, right?

[00:35:01]Hypoventilation, or even lack of hyperventilation, um can kill these patients. So, this is not a, you know, low tidal volume, minimize ventilator induced lung injury patient. This is keep them breathing as high of a minute ventilation as you safely can.

[00:35:16]Pitfall number two, focusing only on salicylate levels. Remember, their symptoms are critical for severity of ingestion. Don't anchor just on the level itself.

[00:35:25]Missing mixed acid-base disorders. If someone comes in and they don't readily tell you they have, you know, consumed excessive salicylates, this can be a tough diagnosis. So, if you see acid-base disorders, even with a normal pH, right? Look at your CO2, look at your bicarb, think about salicylates. Okay, this is critical. Not rechecking salicylate levels is pitfall number four, right?

[00:35:46]Someone might have enteric coated salicylates, someone might have a bezoar, they might have delayed gastric emptying. These levels might go up as time goes on. So, trend the levels, um and use your subspecialist to aid you um in those decisions. And then pitfall number five is forgetting potassium replacement. Remember, hypokalemia will make it very hard to alkalinize the urine.

[00:36:10]So, ensure your potassium is being repleated, um so that you can alkalinize that urine, and try to get them to start to excrete and urinate off some of that um uh salicylates.

[00:36:22]All right, high yield board pearls. Um we're going to leave this here. Again, if you're interested in printing this out, you can annotate it, take it with you, do whatever you want. It's on our Patreon page. We're not going to, you know, spend too much time. We'll just read these, but how you'll uh board pearls for tests. Tinnitus and tachypnea think salicylates on tests.

[00:36:38]Respiratory alkalosis is usually the earliest abnormality. Acidemia worsens CNS toxicity. Hyperventilation is compensatory and protective. Dialysis is the definitive treatment. Trend the salicylate levels serially and make sure potassium is replaced. Right, these are all things that might come up on test questions. And they're good to know to take care of these patients, too.

[00:36:56]Final clinical takeaway before we get into practice questions see what we actually maybe learned. The major physiologic battle in salicylate toxicity is maintaining alkalemia. This prevents CNS salicylate accumulation.

[00:37:12]The sickest patients often deteriorate after acidemia, respiratory fatigue, inadequate ventilation, or delayed dialysis. Recognize this early. Give bicarbonate therapies. Do not intubate them unless you have to. And if you do, goodness forbid, minimize apnea time and ensure you can try to hyperventilate to them on the ventilator. And do not delay dialysis. Dialysis will save lives, okay? When in doubt, dialyze it out.

[00:37:38]All right, let's get into three practice questions. Uh this is the last part of the episode. For those that have not done practice questions with us before, what we will do is we will read the question, we'll read the answer options, and then we'll go right into the answer.

[00:37:49]So, if you need more time, just make sure you pause the episode um because we'll go right into the answer. Um question we go basic, intermediate, advanced in terms of difficulty.

[00:37:57]Question number one. A 24-year-old woman presents after an aspirin overdose. She is tachypnic with a respiratory rate of 32 breaths per minute. Initial blood gas demonstrates a pH of 7.49, PaCO2 of 24, bicarbonate of 19. Which acid-base disturbance is most consistent with salicylate toxicity? A, a pure metabolic acidosis. B, a pure respiratory alkalosis. C, mixed respiratory alkalosis with a metabolic acidosis. Or D, mixed respiratory acidosis and metabolic alkalosis. Pause if you need to. The correct answer is C. Right, salicylate toxicity you tend to get mixed respiratory alkalosis from that increased respiratory drive followed by a combination of an anion gap metabolic acidosis from that lactate creation and ketone creation. All right, so this is the classic acid base pattern. Um the respiratory alkalosis usually happens first followed by a the anion gap metabolic acidosis.

[00:38:57]Um and if you're watching this in video form, we got a longer explanation for the question, but we won't belabor it here.

[00:39:02]All right, question number two, intermediate. A 67-year-old man with chronic salicylate toxicity becomes progressively confused. His pH decreases from 7.46 to 7.33 over several hours.

[00:39:15]Why is this particularly dangerous?

[00:39:18]A, acidemia decreases urinary potassium excretion. B, acidemia increases CNS salicylate penetration. C, acidemia prevents activated charcoal absorption.

[00:39:29]Or D, acidemia decreases serum salicylate levels. Pause if you need to.

[00:39:34]The correct answer is B. Acidemia increases salicylate penetration.

[00:39:40]Remember, non-ionized or neutral salicylate has much better CNS penetration. So, when you get more acidemic, ionized salicylate becomes non-ionized with acidemia, and this then penetrates the CNS more readily.

[00:39:59]All right, last question. We'll just pause the video here so you guys can see the explanation if you want to. Again, pause it so you could read it if you're watching this in video form. All right, last question, question three. And then we will be done. Leave you all to enjoy the rest of your day.

[00:40:14]A 32-year-old woman with severe salicylate toxicity is intubated for worsening agitation. Shortly after intubation, she develops bradycardia and cardiac arrest. And this is like really can happen, everyone. Which mechanism most likely contributed to her deterioration? A, excessive urinary alkalinization. B, rapid decrease in serum potassium. C, loss of compensatory hyperventilation causing worsening acidemia. Or D, increased salicylate protein binding after intubation. Pause if you need to. The correct answer is C, loss of compensatory hyperventilation causing worsening acidemia. Um as we said, right, intubating these patients is so high risk cuz no matter how hard you try, um it's really hard to not lead to any degree of hypoventilation or apnea, right? You can do awake intubations, you can do all this stuff, and you know, certainly there's approaches that will decrease this risk, but it's really hard to maintain a patient's minute ventilation when they're already breathing like crazy um while putting an endotracheal tube in.

[00:41:12]And this can cause worsening acidemia even briefly, which can lead to more CNS penetration and honestly sudden cardiac arrest. This is something that does happen, which is why we really try to avoid these patients uh intubating these patients if we have a choice. And again, just like before, we'll leave uh the longer explanation here if anyone would like to pause and read it.

[00:41:32]All right, that is all we have for you today. Thanks for checking out the episode. Let us know what thoughts, comments, questions you have down below.

[00:41:38]We are so stoked about our YouTube community and Patreon community. So, if you want to join those, we'd love to have you. Um check them out. Um and either way, stay well, keep learning, and we hope to see you next time.

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