Ep 180 Acetaminophen Poisoning – Pitfalls in Assessment and Management

Metadata

• Author: Emergency Medicine Cases
• Full Title: Ep 180 Acetaminophen Poisoning – Pitfalls in Assessment and Management
• Category: #podcasts
• URL: https://share.snipd.com/episode/7744b889-8c12-4cac-b68c-9b869f0b1949

Highlights

• Episode AI notes
  1. Blood work abnormalities are critical in determining the management of acute drug overdose cases, especially concerning the stages of acetaminophen toxicity, where acetaminophen levels should be high and liver function tests should be normal. Patients with an increase in transaminases by the 24-hour mark are at risk for liver damage from the overdose.
  2. False positive elevations in acetaminophen levels can result from bilirubin interference and elevated INR results that can be temporary and later normalized. It's essential to consider other indicators of health, such as the levels of bilirubin, to avoid potential misdiagnoses.
  3. Acetaminophen overdose cases can include misinterpretations of liver enzymes, resulting from false-positive levels, high bilirubin, and only having ALT instead of AST. While a delay in hepatic failure cases can cause elevated bilirubin, it's critical not to miss potential cases due to limited test results.
  4. Toxicologists use ALT and AST levels to monitor patients with an acetaminophen overdose. Patients should be monitored with serial ALT levels to catch any delayed hepatic toxicity, while AST provides a better indication of patient recovery.
  5. Hyperphosphatemia is an excellent prognostic test for patients with acetaminophen overdose, while low serum phosphate levels suggest a higher chance of survival. Although the hyperphosphatemia can be useful, some pitfalls can affect the data's interpretation that would help assess the patient's condition and acute liver failure risk.
  6. After an acetaminophen exposure, draw an acetaminophen level after 4 hours and use the Matthew Rheumach nomogram to determine treatment. Early activated charcoal use is crucial, especially with pediatric patients who may have accidentally ingested the drug.
  7. For massive acetaminophen ingestion, the patient requires prompt treatment. The level of toxicity defines the timing of the treatment, especially those coming in later who require immediate attention.
  8. Dialysis is not a standard of care for acetaminophen poisoning but indicated where it's causing toxicity, such as lactic acidosis or depressed level of consciousness. Hemepisol shows potential benefits as a more effective treatment for acetaminophen overdose than NAC and provides different benefits.
  9. Fumepisol shows promising results and may be more important in the future than NAC, given its potential for blocking the formation of NAP-key and inhibiting proteins that cause cellular necrosis. (View Highlight)
• The stages of acetaminophen toxicity
  Key takeaways:
  • Acetaminophen levels should be high at the first stage of overdose, and then decrease as the overdose progresses.
  • Liver function tests should be normal at the first stage, but may increase later on.
    Transcript:
    Speaker 1
    Maybe one other thing to mention in the stages is when we start to see abnormalities in the blood work and what those are, that's a helpful pearl that I find I actually apply all the time when I'm managing these cases. So let's take a patient, for example, who the most straightforward one is going to be a patient who has that acute one-time overdose. So I'll use me as an example. I was having a hard time. I take 100 tablets of 325 milligrams of Tylenol and a one-time ingestion and I'm going to present to hospital, which is six hours after taking that ingestion. I'll be in stage one right now and as Margaret said, I might have a bit of nausea and vomiting. And appropriately, somebody assessing me would probably go ahead and draw a serum acetaminophen level and also liver function tests and transaminases. So we can talk about that a little bit more. At this sort of first stage, what I'm presenting six hours after, my acetaminophen level you would expect to be elevated, but there will be no elevation in my transaminases. My AST and ALT will probably be completely normal. As you move on into the later stages, as early as 12 hours, but probably closer to 24 hours, you start to see your transaminases increase. And so if I'm this patient who actually, instead of presenting six hours later, maybe presents the next morning or 24 hours later, at that point, my acetaminophen may be undetectable, but I may have elevation in my transaminases, maybe an AST of 300 or 400, an ALT of maybe 200 or 300 or 300, you know, a little bit less.
    Speaker 2
    Okay, so the bottom line there is that early on, you expect the acetaminophen level to be high, and then later on it decreases, whereas with your liver enzymes, initially, they'll be normal and then increase. (Time 0:11:34)
• What to Look for in a Patient With Acetaminophen Overdose
  Key takeaways:
  • Every patient who takes an acetaminophen overdose will have a bump in their AST, ALT, and their transaminases by the 24 hour mark.
  • If a patient's liver enzymes are not going to be fine and they are going to go on to hepatotoxicity, they will have started to bump, and their levels may be rising by the 24 hour mark.
    Transcript:
    Speaker 3
    Right, and so every patient who has taken an acetaminophen overdose that is going to go on to hepatotoxicity is going to have a bump in their AST, ALT, their transaminases by the 24 hour mark. It won't be the peak, but they will start to go up. So the reason to get initial liver enzymes and find out that your AST is 23 or 29 is so that at the 24 hour mark, you'll see it's still 23 or 29, they're going to be fine. If they're not going to be fine and they're going to go on to hepatotoxicity, they will have started to bump, and they may not be 100 yet. They may be 99, but they will start to rise by the 24 hour mark for every patient.
    Speaker 2
    That's a good nuanced clarification.
    Speaker 3
    There's another pearl. Acetaminophen concentration is interfered with by bilirubin. And so if you present with hepatotoxicity, liver enzymes that are elevated, a high bilirubin, etc., your acetaminophen level may be positive because there's a colorometric interference with high bilirubin levels.
    Speaker 1
    So if you present with a hepatitis, for example, an infectious hepatitis and have an elevated bilirubin, your serum acetaminophen concentration may be detectable when in fact it's actually because of your infectious hepatitis. (Time 0:13:42)
• False Positive Elevates Acetaminophen Level
  Key takeaways:
  • There are two pearls that can interfere with the accuracy of an acetaminophen level measurement.
  • One is due to the presence of bilirubin, and the other is due to the elevated levels of the enzyme INR.
  • If a person presents with hepatotoxicity, their acetaminophen level may be elevated even if the true cause of the elevated level is something else.
    Transcript:
    Speaker 3
    There's another pearl. Acetaminophen concentration is interfered with by bilirubin. And so if you present with hepatotoxicity, liver enzymes that are elevated, a high bilirubin, etc., your acetaminophen level may be positive because there's a colorometric interference with high bilirubin levels.
    Speaker 1
    So if you present with a hepatitis, for example, an infectious hepatitis and have an elevated bilirubin, your serum acetaminophen concentration may be detectable when in fact it's actually because of your infectious hepatitis.
    Speaker 2
    So that's one example of a false positive elevates acetaminophen level is just if you have hyperbiliary but anemia for any other reason. Right. Got it.
    Speaker 3
    The other pearl is that when you have a very high acetaminophen level on first presentation. So Emily, when she presents at the six hour mark, has an acetaminophen level that's 2,000, for example, because of what she took, her INR will also be elevated at that time, too, because there's an interference of acetaminophen with the INR assay. And that INR then goes back down to normal. (Time 0:14:32)
• The Pitfalls of Bilirubin Elevations in Acute Acetaminophen Overdoses
  Key takeaways:
  • There are potential pitfalls with using acetaminophen levels as the sole indicator of a person's health status after an acetaminophen overdose.
  • It is important to also look at other indicators of health, such as the levels of bilirubin, to make sure that someone who has overdosed on acetaminophen does not go on to develop late fulminative hepatic failure.
    Transcript:
    Speaker 3
    So I think we've already talked about the possibility of having a false positive acetaminophen level. If your bilirubin is high and in the setting of an acute acetaminophen overdose, we never see a bilirubin that's over 100. At the time that they've got the late fulminative hepatic failure, bilirubins can be elevated somewhat but never sky high that they would interfere with acetaminophen levels. So that's one pitfall. Another pitfall may be that your lab is only able to give you an ALT. And an ALT does go up a little bit later than does the AST. So we want to be sure that we don't miss somebody who is going to go on to hepatic failure because we only have an ALT. (Time 0:22:31)
• The Pitfalls of Only Having an ALT Available to Detect Acetaminophen Overdose
  Key takeaways:
  • Bilirubin levels can be elevated in the setting of an acetaminophen overdose, but they are never high enough to interfere with the level of acetaminophen in the blood.
  • Bilirubin levels can be measured with an ALT or AST, and if the level is high, the patient may need to be monitored for a delayed hepatic toxicity.
    Transcript:
    Speaker 3
    So I think we've already talked about the possibility of having a false positive acetaminophen level. If your bilirubin is high and in the setting of an acute acetaminophen overdose, we never see a bilirubin that's over 100. At the time that they've got the late fulminative hepatic failure, bilirubins can be elevated somewhat but never sky high that they would interfere with acetaminophen levels. So that's one pitfall. Another pitfall may be that your lab is only able to give you an ALT. And an ALT does go up a little bit later than does the AST. So we want to be sure that we don't miss somebody who is going to go on to hepatic failure because we only have an ALT. And so for those patients, we might have to do serial ALT levels for up to 24 hours after an exposure to be sure that they're not going to go on to a delayed hepatic toxicity. And the ALT will take a lot longer to fall after you've been treating your patient because it's half-life in the serum is a lot longer. So we have toxicologists like an AST because it goes up first a little bit sooner than the ALT. And it falls faster so that we know that the patient's recovering faster than if we only have an ALT available. That being said, if we only have an ALT, we'll take it. (Time 0:22:31)
• Acetaminophen toxicity: what to do when you see a rise in ALT levels
  Key takeaways:
  • Acetaminophen has a longer halflife in the blood than the ALT, so it will take longer for the ALT to fall after treatment has been started.
  • If acetaminophen is taken in a slow release form, a fourhour acetaminophen level should be repeated at the 8-hour and 12-hour marks.
  • If a delayed release preparation of acetaminophen is taken, a repeat acetaminophen level should be done at the 8hour and 12-hour marks.
    Transcript:
    Speaker 3
    And the ALT will take a lot longer to fall after you've been treating your patient because it's half-life in the serum is a lot longer. So we have toxicologists like an AST because it goes up first a little bit sooner than the ALT. And it falls faster so that we know that the patient's recovering faster than if we only have an ALT available. That being said, if we only have an ALT, we'll take it. We also know that there's certain preparations of acetaminophen that are either slow release in and of themselves. So all 650 milligram tablets of acetaminophen are a delayed release formulation. So the first 325 milligrams is released in the stomach basically. And the second 325 milligrams is released in the small bowel. And so the drug has to go to the small bowel before the inner coating is dissolved in the second 325 milligrams of acetaminophen are released. And because of that, sometimes we have patients who are line-crossers. So when we usually recommend doing a four-hour acetaminophen level, like you suggested in the initial investigation of that acetaminophen poison patient, we would recommend a repeat acetaminophen level at the eight-hour and the 12-hour mark if they've taken a delayed release preparation of acetaminophen. (Time 0:23:28)
• The Hyperphosphatemia: Worth Ordering and How to Interpret It
  Key takeaways:
  • There are many pitfalls in interpreting blood work for acetaminophen toxicity,.
  • The hyperphosphatemia is the best prognostic test for acute liver failure, assuming that the patient doesn't have already AST through the roof, ALT through the roof, and INR through the roof.
    Transcript:
    Speaker 2
    Right, yeah, two things I want to touch on there. First is other pitfalls in interpreting the nomogram. And the other thing is the hyperphosphatemia. I've read a little bit about this in preparation for this. The hyperphosphatemia is the best prognostic test, assuming that the patient doesn't have already AST through the roof and ALT through the roof and INR through the roof. Those will be obvious, but why don't we start with the hyperphosphatemia one, whether it's worth ordering and if we do order it, how to interpret it. And then what the evidence for that is, and then we can talk about the nomogram some more.
    Speaker 1
    So when we're dealing with acetaminophen, there's so many different things to think about, because what Margaret's just gone over are some of the pitfalls and interpretation of blood work for making decisions about which patient we need to be concerned about, i.e., which patient do we need to treat with NAC? And then there's a whole other set of considerations which are, which patients do we think are going to go on to develop acute liver failure that they won't survive from? And that's a sort of separate set of considerations. (Time 0:26:02)
• The Importance of Serum Phosphate in Acute Liver Failure
  Key takeaways:
  • There are many different tools that can be used to predict a patient's prognosis, and one of those tools is serum phosphate.
  • Serum phosphate is one of those tools that has been shown to be helpful in predicting a patient's prognosis, and it is important to know this information early on in order to make better decisions about care.
    Transcript:
    Speaker 1
    That prognostication, there's lots of different work that's been done to figure out what's the best tool to use, and the serum phosphate has been one of those tools that has been used because a study showed that when you have acute liver failure with a high serum phosphate, you had a higher chance of dying without transplant. So, you know, I think that if you are seeing a patient who said, I'm coming in, and I have actually seen this patient, I should say, so they definitely exist. I've seen them at the bedside myself. If you are seeing a patient who said, let's say it's a Sunday, and the patient said, on Friday night, I took a bunch of Tylenol, and this patient's coming in with abdominal pain and you order transaminases and an INR and an acetaminophen and the transaminases in my patient's case. I'd never seen an AST of 37,000 before, I had an AST of 37,000 and an INR of six. A serum phosphate would be a very helpful measurement in this patient. It would be a useful data point, I would say. It's not going to influence us, but it's a useful data point because we know that when that serum phosphate is higher, that patient has a lesser chance of survival. And part of the theory about this is that if the serum phosphate is low, maybe it's because there's some regeneration happening and the cells are using that phosphate.
    Speaker 2
    I imagine that's an important piece of information to know early if (Time 0:28:02)
• Acetaminophen level and treatment
  Key takeaways:
  • Acetaminophen levels should be drawn at the fourhour mark after exposure, or as soon as the patient presents to the hospital.
  • Acetylcysteine should be given to patients who are below the treatment line.
  • Patients who have taken opioids or anticholinergics in combination with acetaminophen should be treated even if their acetaminophen level is below the treatment line.
    Transcript:
    Speaker 3
    As it was meant to be used. So if you have a patient who declares to you that they've taken a single one-time overdose of acetaminophen, whether that be your child who's gotten into the liquid and you're in the wild and all and drank the whole bottle, or whether that be an adult who develops nausea and vomiting and regrets what they've done and presents to the emergency department, you draw an acetaminophen level at the four-hour mark after their exposure, or as soon as they present a hospital, if it's later than that, and you plot that acetaminophen level against time on the Matthew Rheumach nomogram. Over the treatment line, they get an acetylcysteine, and if they're below the treatment line, except in the patient who has taken a preparation that's with an opioid, with an anticholinergic, or is a delayed release, you can plot that on the line and you can decide treatment or no treatment. For the patient who's taken those preparations in combination with an opioid or an anticholinergic or their slow release, you might have to draw a level again at the eight-hour mark and the 12-hour mark before you are sure that you've reached the peak and that the patient doesn't need treatment. But otherwise, you should interpret an acetaminophen level that is positive, i.e. That's greater than 66 micromoles per liter, or 10 milligrams per deciliter. If you find an acetaminophen level that is positive, then you should treat that patient because all other scenarios are the delayed presentations or the staggered presentations or the unintentional that we would have missed for some other reason.
    Speaker 1
    Rheumach mathian overgrams super awesome, but we can really only use it in such a narrow spectrum of acetaminophen toxic presentations.
    Speaker 3
    I guess the other important point is it can only be used up to 24 hours after the exposure. (Time 0:31:55)
• Acetaminophen Levels in Self-Harming Patients
  Key takeaways:
  • Acetaminophen levels peak at about the two and a half hour mark and start to be redistributed by the four hour mark.
  • This is why it is important to do a four hour acetaminophen level.
    Transcript:
    Speaker 3
    So I would suggest using activated charcoal in the early presenter. So that's the patient who comes to the emergency department soon after their exposure. And that's most often the pediatric patient who parents identify that all of the container is missing. Because the self-harming patient is not likely to come in unless they have a change of heart or unless they have GI upset. Early enough in their presentation for the acetaminophen distill be in the GI tract. We think that acetaminophen concentrations will peak at about the two and a half hour mark and start to be redistributed by the four hour mark. And that's why we suggest doing a four hour acetaminophen level. (Time 0:44:24)
• Acetaminophen Levels in Self-Harming Patients
  Key takeaways:
  • Acetaminophen can be harmful if taken too soon after exposure, and activated charcoal can help to bind the drug and reduce its effects.
  • The dose of activated charcoal should be 10 times the amount of the drug that was ingested.
    Transcript:
    Speaker 3
    So I would suggest using activated charcoal in the early presenter. So that's the patient who comes to the emergency department soon after their exposure. And that's most often the pediatric patient who parents identify that all of the container is missing. Because the self-harming patient is not likely to come in unless they have a change of heart or unless they have GI upset. Early enough in their presentation for the acetaminophen distill be in the GI tract. We think that acetaminophen concentrations will peak at about the two and a half hour mark and start to be redistributed by the four hour mark. And that's why we suggest doing a four hour acetaminophen level. And if they're there four hours afterwards, most of the acetaminophen's probably been absorbed. And that's except the patient who has the delayed release preparation or is taken out with an opioid or with an anti-colonergic medication. But it would be reasonable to give activated charcoal up to two hours after the exposure if it's documented well what time it was. And the dose of activated charcoal is theoretically supposed to be ten times the amount of the drug that was ingested so that there's adequate binding. But when we're talking about acetaminophen, these are big tablets. (Time 0:44:24)
• Acetaminophen and Activated Charcoal: A Decontaminating Dose
  Key takeaways:
  • Acetaminophen can be harmful if taken in high doses or if it is taken with other medications that can slow down its absorption.
  • Activated charcoal can help to remove the acetaminophen from the body, and can be given up to two hours after the exposure.
    Transcript:
    Speaker 3
    So I would suggest using activated charcoal in the early presenter. So that's the patient who comes to the emergency department soon after their exposure. And that's most often the pediatric patient who parents identify that all of the container is missing. Because the self-harming patient is not likely to come in unless they have a change of heart or unless they have GI upset. Early enough in their presentation for the acetaminophen distill be in the GI tract. We think that acetaminophen concentrations will peak at about the two and a half hour mark and start to be redistributed by the four hour mark. And that's why we suggest doing a four hour acetaminophen level. And if they're there four hours afterwards, most of the acetaminophen's probably been absorbed. And that's except the patient who has the delayed release preparation or is taken out with an opioid or with an anti-colonergic medication. But it would be reasonable to give activated charcoal up to two hours after the exposure if it's documented well what time it was. And the dose of activated charcoal is theoretically supposed to be ten times the amount of the drug that was ingested so that there's adequate binding. But when we're talking about acetaminophen, these are big tablets. 325 milligrams, 500 milligrams, 650 milligrams. And people take large amounts of acetaminophen. And so we're practically never going to get them to take ten bottles of activated charcoal, for example, to be able to give that ten to one drug ratio. So it's probably reasonable to give them a decontaminating dose of one to two bottles of activated charcoal. So 50 to 100 grams for the average adult size patient. (Time 0:44:24)
• NAC for Massive Acetaminophen Ingestions
  Key takeaways:
  • Anton says that defining what a massive ingestion is, and specifically just in terms of the number of tablets taken, is tough.
  • Anton recommends waiting to get a level within eight hours in order to make treatment decisions.
  • If NAC is started within about eight hours of a single acute ingestion, people do great.
    Transcript:
    Speaker 1
    Anton, I know we're going to talk about massive presentations in a few minutes, but I think that the trick for me when you ask this question is that defining what a massive ingestion is, and let's say specifically just in terms of the number of tablets taken, is tough. We don't really know this. I have a patient in front of me who's alert and oriented, conversing with me pretty stable vital signs that telling me they took, and I'm being obviously facetious here, but 100 kilos of Tylenol two hours ago. I am not looking at that patient and thinking that they fit the paradigm or the toxidrome of a massively acetaminophen poison patient. And in my mind, I think, I'm going to wait to get a four-hour concentration to see what's going on. If that concentration is under the line, maybe I'll order a six-hour concentration or an eight-hour concentration to make sure, because we're talking about such a huge overdose potentially, that it doesn't go over the line, like Margaret said, the delayed absorption. But what we know with NAC is that if we get NAC started within about eight hours of a single acute ingestion in general, people do great. And so there aren't a lot of scenarios when somebody is able to talk to us that I wouldn't recommend necessarily getting a level within eight hours and making treatment decisions there. As I say this, I'm like star, star, star. (Time 0:50:36)
• NAC: A Drug of Last Resort
  Key takeaways:
  • There are many exceptions to the rule that patients should be treated with NAC as soon as they are admitted to the hospital with suspected liver toxicity.
  • There are potential adverse effects to NAC treatment, including anaphylactic reactions.
    Transcript:
    Speaker 3
    There's so many exceptions to this. And if that patient came in at the 16-hour mark, you would start the NAC right away because time is liver. But if they come in at the four-hour mark, you can afford to wait for that level to come back to decide whether or not they need to be treated.
    Speaker 1
    And we say this because we see patients that end up not requiring treatment, that have given us a history where they say they took something. And based on that clinical course, it just doesn't end up being accurate or reflective that whatever they took will lead to hepatotoxicity.
    Speaker 3
    And there's adverse effects to NAC, so we don't want to give it to everybody.
    Speaker 1
    But almost everybody.
    Speaker 2
    And those adverse effects are?
    Speaker 3
    There's an anaphylactoid reaction documented with NAC, which means you get histamine release based on the speed of the infusion of the anacetylzysidine. (Time 0:51:59)
• What is Massive Overdose?
  Key takeaways:
  • Always speak to your poison center about the dosing, but also work with your local teams to make sure that there's an IV protocol that everyone can agree on.
  • If your IV protocol happens to jibe with what your poison center is suggesting, great. If it doesn't, you can make the appropriate adjustments.
  • And poison center has helped hospitals develop their protocols.
    Transcript:
    Speaker 2
    How about this as a take home message? Always speak to your poison center about the dosing, but also work with your local teams to make sure that there's an IV protocol that everyone can agree on. And before you click the IV protocol, speak to your poison center. And if your IV protocol happens to jibe with what your poison center is suggesting, great. And if it doesn't, you can make the appropriate adjustments.
    Speaker 1
    And I think our poison center has helped hospitals develop their protocols and stuff like that. So if you're listening and you're in a position to make that happen to your hospital, it's worthwhile to reach out and contact us.
    Speaker 2
    All right, let's talk about massive overdose. I want to talk about the definition of massive overdose, the presentation, and the treatment of massive overdose. We've already touched a little bit on what massive overdose is, but I want to get into it a little bit more. So first of all, how do we define massive overdose? And when should we suspect a massive overdose?
    Speaker 3
    So I think we alluded to this before. Literature is not very helpful on that, but somewhere over 500 milligrams per kilogram is suggested as being the definition of a massive overdose. (Time 1:01:58)
• The Pathophysiology of Massive Overdoses
  Key takeaways:
  • Massive overdoses can be defined clinically by the presence of lactic acidosis, decreased LOA, and hypothermia.
  • The toxidrome that is seen in massive overdoses is different from the toxidrome seen in other overdose patients.
    Transcript:
    Speaker 2
    So that's in terms of the amount taken. What about in terms of clinically? How would you define a massive overdose in terms of clinically? You know, there's lactic acidosis, there's decreased LOA, hypothermia.
    Speaker 1
    So the massive overdose patient is something that I like to think of is actually a very distinct toxidrome from what we've been speaking about earlier. And that's because we think that what's happening in terms of the pathophysiology is a little bit different in the massive overdose patient than it is in all the rest. The patients that I'm concerned about who take a massive overdose, Margaret's given us a 500-meg per kilo, for example, take that overdose, may fit this toxidrome. And this toxidrome looks like a patient who is altered, often comatose, like GCS, you know, six or something, who has evidence of a metabolic acidosis with an elevated lactate. And what's happening here is that the acetaminophen parent compound and the NACCHE as well are interacting with one of the enzymes in oxidative phosphorylation and our electron transport chain and affecting the way energy is being produced in our cell. (Time 1:03:16)
• Different presentations of acetaminophen overdose
  Key takeaways:
  • Massive overdoses are a separate toxidrome with different treatment considerations.
  • Transaminases in a massive overdose are usually rock solid normal, but may be elevated in a regular overdose.
    Transcript:
    Speaker 1
    The single acute ingestions that come in generally don't look like that. This patient looks different, you know, they're found unconscious.
    Speaker 2
    All right. Great. So it's nice just to understand, I think, on a very general level. It's almost like two totally different toxidromes, two different kinds of patients, two different presentations.
    Speaker 1
    This massive overdose patient I just talked to you about, they're transaminases. This LF, like your ALT, could be like 19. The transaminases are rock solid normal.
    Speaker 2
    Wow. So very different. And again, to reiterate what you had mentioned before, distinctly uncommon. Maybe the poison center in Ontario sees one a month. So now that we've defined massive overdose and given you a sense that it's really a separate toxidrome, and the differences between a massive overdose and a regular overdose, let's talk about the treatment considerations of a massive acetamin overdose and how they're different. So the one thing we already talked about was charcoal, and that you might extend that cut off of one to two hours to four hours for a massive overdose.
    Speaker 3
    And this is a patient you're going to have to intubate before you can give them that charcoal, because they're so altered. Right. (Time 1:05:37)
• Dialysis for Acetaminophen Poisoning
  Key takeaways:
  • Hemodialysis is not a standard of care for acetaminophen poisoning.
  • Dialysis can effectively clear acetaminophen from the body faster than other methods.
    Transcript:
    Speaker 2
    So we've talked about charcoal. We've talked about NAC dosing. With charcoal, we might give it up to four hours. And with NAC in your massive overdose, it'll be a higher dose. Let's move on to hemodialysis. And I'll just simply ask, what are the indications for hemodialysis in acetaminophen poisoning?
    Speaker 3
    So I don't think hemodialysis is a standard of care. If you have a patient who is a massive overdose, and you think that the acetaminophen parent is responsible for at least some of the toxicity, for the lactic acidosis, for the depressed level of consciousness, then we want to get rid of the acetaminophen. And acetaminophen has got some normal roots of metabolism, but it's fairly slow as compared to how long it's going to take us to get rid of that massive amount of acetaminophen. And we could clear it from the serum faster with dialysis. It's one of those compounds that's got a small volume of distribution. It's very water-soluble. It's a small molecule. It will cross dialysis membranes. So, yes, we can effectively dialize out acetaminophen parent. (Time 1:08:15)
• The Differences Between Hemepisol and NAC for Acetaminophen
  Key takeaways:
  • There is evidence that hemepisol can be more beneficial than just giving NAC when treating acetaminophen overdose.
  • Hemepisol can halt the formation of NAPkey, which is important because NAC doesn't do this.
    Transcript:
    Speaker 1
    You know, Anton, I don't have a clear answer for this right now, and I accept that. I know it's so annoying, but I think that this is really cool stuff, and I think it's really important for all of us in the Emergency Medicine community. To know about this, it's going to be coming out in the next, I don't know, 10 years. We'll have more concrete information. Where we're at right now with hemepisol for acetaminophen is that there's evidence in animal studies, human volunteer studies, and case series that patients who are treated with hemepisol get a bit more benefit and in a different way than just giving NAC. Let me just explain this for one more minute. Fumepisol does two things, and it does different things than NAC. One thing Fumepisol does is halt the formation of NAP-key. NAC doesn't do that, but Fumepisol blocks the CIP-2E1 enzyme that metabolizes acetaminophen to NAP-key. (Time 1:11:19)
• The Effect of Hemepisol on Acetaminophen Pharmacokinetics
  Key takeaways:
  • Hemepisol may be more beneficial than NAC in the treatment of acetaminophen overdose.
  • More research is needed to confirm these findings.
    Transcript:
    Speaker 1
    You know, Anton, I don't have a clear answer for this right now, and I accept that. I know it's so annoying, but I think that this is really cool stuff, and I think it's really important for all of us in the Emergency Medicine community. To know about this, it's going to be coming out in the next, I don't know, 10 years. We'll have more concrete information. Where we're at right now with hemepisol for acetaminophen is that there's evidence in animal studies, human volunteer studies, and case series that patients who are treated with hemepisol get a bit more benefit and in a different way than just giving NAC. Let me just explain this for one more minute. Fumepisol does two things, and it does different things than NAC. One thing Fumepisol does is halt the formation of NAP-key. NAC doesn't do that, but Fumepisol blocks the CIP-2E1 enzyme that metabolizes acetaminophen to NAP-key. The second thing, and this is super cool, but the second thing that it seems like Fumepisol does is act at a downstream site in the pathway of cellular necrosis to inhibit some of the proteins from getting activated on that pathway. What that means is maybe somewhere down the pathway where necrosis is already happening, that pathway gets blocked by Fumepisol, again, in vitro stuff.
    Speaker 3
    Basically, NAP-key has already been formed. (Time 1:11:19)