CEimpact Podcast

New Guidelines for Acetaminophen Poisoning

September 11, 2023 CEimpact
New Guidelines for Acetaminophen Poisoning
CEimpact Podcast
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CEimpact Podcast
New Guidelines for Acetaminophen Poisoning
Sep 11, 2023
CEimpact

N-Acetyl Cystine (NAC) has been long used as the antidose for acetaminophen poisonings - although with variable implementation. Join host, Geoff Wall, and guest, Kayla Myers, discuss a new consensus guideline for appropriate treatment of acetaminophen overdose.
 
The GameChanger
NAC should be used if any doubt of acetaminophen poisoning based on new consensus guidelines. NAC may be used continued beyond standard dosing for chronic or high amounts of acetaminophen.
 
Host
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health

Guest
Kayla Myers, PharmD
Clinical Pharmacist
Unity Point

Reference
Dart RC, Mullins ME, Matoushek T, et al. Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement. JAMA Netw Open. 2023;6(8):e2327739. doi:10.1001/jamanetworkopen.2023.27739

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062

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CPE Information
 
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Apply the new modified Rumack-Matthew nomogram to a potential acetaminophen poisoning
2. Discuss the use of fomepizole in the use of acetaminophen overdose

0.05 CEU/0.5 Hr
UAN: 0107-0000-23-300-H01-P
Initial release date: 9/11/2023
Expiration date: 9/11/2024
Additional CPE details can be found here.

Follow CEimpact on Social Media:
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Show Notes Transcript Chapter Markers

N-Acetyl Cystine (NAC) has been long used as the antidose for acetaminophen poisonings - although with variable implementation. Join host, Geoff Wall, and guest, Kayla Myers, discuss a new consensus guideline for appropriate treatment of acetaminophen overdose.
 
The GameChanger
NAC should be used if any doubt of acetaminophen poisoning based on new consensus guidelines. NAC may be used continued beyond standard dosing for chronic or high amounts of acetaminophen.
 
Host
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health

Guest
Kayla Myers, PharmD
Clinical Pharmacist
Unity Point

Reference
Dart RC, Mullins ME, Matoushek T, et al. Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement. JAMA Netw Open. 2023;6(8):e2327739. doi:10.1001/jamanetworkopen.2023.27739

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062

Pharmacist Members, REDEEM YOUR CPE HERE!
 
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)


CPE Information
 
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Apply the new modified Rumack-Matthew nomogram to a potential acetaminophen poisoning
2. Discuss the use of fomepizole in the use of acetaminophen overdose

0.05 CEU/0.5 Hr
UAN: 0107-0000-23-300-H01-P
Initial release date: 9/11/2023
Expiration date: 9/11/2024
Additional CPE details can be found here.

Follow CEimpact on Social Media:
LinkedIn
Instagram

Speaker 1:

Welcome to the Game Changers podcast, where we have clinical conversations that impact your pharmacy practice. Let's listen in as our team discusses this week's clinical practice game changer.

Speaker 2:

Hello and welcome to Game Changers clinical conversations. I'm your host, jeff Wall, professor of pharmacy practice at Drake University and internal medicine clinical pharmacist at Methodist Hospital in Des Moines. Today I'm happy to welcome a guest star. We don't have as many of those as I like and I appreciate those who do come on and we have a new guest star and I'm excited to have her here. Dr Kayla Myers is one of our emergency room clinical pharmacy specialists here at Methodist and I am grateful that she took the time out to do the podcast. So welcome to the podcast, kayla.

Speaker 3:

Thank you, glad to be here.

Speaker 2:

Good and with her expertise in emergency medicine, this is going to come in real handy, because today's topic is going to be the brand spanking new American and Canadian joint guidelines on the treatment of acetaminophen overdose and to my knowledge, this is the first attempt at a unified set of guidelines for acetaminophen poisoning. I'm trying to rack my brain and in the research I did leading up to this I'm like has anyone ever really come up with like actual formal guidelines that were endorsed by you know, either you know the poison control center group or somebody else, and I couldn't find one. And God knows, I've been dealing with Tylenol overdoses most of my career and I don't ever remember there ever being some official guidelines. So this is a pretty big deal if you work in emergency room medicine, if you work in an ICU or you're working in toxicology. That this kind of joint guideline to be done that tries to take a look at kind of the evidence based surrounding what we do for acetaminophen overdose is probably long overdue and they actually note that in the text of the guideline. So you know, we'll talk a little bit about that. We'll talk about some of the things I've seen over the years that have kind of maybe shake my head or scratch my head when it comes to see them in overdoses. And again, grateful to Dr Myers being here to kind of give us her perspective. So you know, if you work in the emergency room or or an ICU any hospital, you know that we still see plenty of acetaminophen overdoses in the United States and in fact, the paper notes that in 2021, us poison control center received more than 80,000 cases involving an acetaminophen product.

Speaker 2:

Now, of course, all those were severe overdoses that required to go to the emergency room or the ICU, but you're still going to see this very, very commonly. It is in Canada. It is responsible for about 4,500 hospitalizations every year, according to the paper. That number seems low to me in the United States. I suspect it is a far higher number in the United States that we see, but the bottom line is that is that acetaminophen overdose is still really quite common and, despite what I think the lay public thinks, is quite deadly. And we all know that acetaminophen can be toxic to the liver, but it's worth noting that it can also cause significant mitochondrial dysfunction that can lead to lactic acidosis and all sorts of other problems as well. So you know, bottom line is that is that it's common. It is much more serious than I think that the lay public thinks it is and it's. It's easy to even accidentally overdose because of course you know there is acetaminophen in just about every product you go to a community pharmacy for you may get a cold product it's got acetaminophen in it. You're taking something for sciences, it's got acetaminophen in it, etc. Etc. So a lot of times patients aren't even aware that what they're taking contains acetaminophen and of course that leads to things like chronic overdoses where people are consistently taking over four grams a day of Tylenol. So it is worth noting that the estimate suggests that between four and 600 people die every year from acetaminophen overdoses and I've never seen any solid data on number of transplants, but it obviously has got to be higher than that. Number of that are due to basically acetaminophen poisoning.

Speaker 2:

So the paper notes, the guideline notes that again, you know there's been a number of changes in how we deal with acetaminophen poisoning in the last, you know, 25, 30 years. When I came out of school there was no such thing as adrenalin and acetalcysteine for example, things along those lines. So they felt like a dedicated guideline that brought together the American Academy of Clinical Toxicology, the American College of Medical Toxicology and both the United States and Canadian Association of Poison Control Centers. So you know, I've obviously the experts in this field. As you might imagine, they used the amodified Delphi method, which is pretty much standard now for all guidelines. That created a decision framework and they basically asked Pico type questions, at which case then they looked for evidence to support those answers and they used something I've not had to do a little research on called the Squire framework. I've heard of the Prisma and some other frameworks, but this is another, you know, framework for writing evidence-based guidelines. It certainly makes sense.

Speaker 2:

It's worth noting that, because we're dealing with poisons, you're not going to see randomized control trial data almost at any time, right? So I mean you know this is largely going to be case series, retrospective case control studies, things along those lines. So it's worth noting that the evidence level is probably not what up to you're going to see in some other guidelines, just because, again, because of the nature of toxicology, it's not either practicable or really feasible to do randomized control trials. Largely so they note that in their literature search, in fact, they only found that seven articles met evidence quality, and only of those, only one wasn't actually properly conducted and powered randomized control trial. So, again, not surprising. And that doesn't mean it's a bad set of guidelines. It just means that compared to, I think, a lot of the other guidelines we think about, especially in the worlds of cardiology and infectious diseases and stuff that there's, the evidence base is probably a little bit smaller.

Speaker 2:

So they talk about first about the Rubik Matthew Nama Graham. When I talk about acetaminophenobre doses to my students or residents I always say that it's kind of a federal law that whenever you talk about acetaminophenobre doses you have to show them the Rubik Matthew Nama Graham. I was heartened, I have to be, because I've always been of the opinion that the Rubik Matthew Nama Graham was largely useless because of the way it was set up. They don't go quite that far but they do note that it's probably used incorrectly the vast majority of the time. They note that the nomogram is really only applies for acute ingestions within a certain timeframe and that it doesn't really account for extended release preparations. It doesn't really account for super high ingestions, things along those lines I said I've never been a big fan of the Rooting Ethnomogram.

Speaker 2:

Honestly, I would basically tell my residents look if you suspect a C2M poisoning and their levels above 20, which is kind of the minimum level on the Rm nomogram, feel free to treat because again, when in doubt, treat is always the watchword. I was heartened to see that in the new set of guidelines that they actually modified the Rooting Ethnomogram, I think, to make it a lot easier to read and a lot easier to basically make clinical decision making. They'll have a link of course, the guidelines, which are free in our show notes. But the way the Rm nomogram is set up now is that if there's none of this cross lines and stuff like that, they have basically a single line for treatment and a single line that considers patients who have a high risk ingestion. They also note that the vast majority of time we don't know exactly when patients took a C2M and so they note that in their start and stopping rules for anesthetical assisting that we'll talk about here in just a second.

Speaker 2:

Some of the other definitions they use in the guidelines. They define a high risk acetaminophen ingestion as someone who's ingested at least 30 grams of acetaminophen. Sounds like a lot, but when you think about it, if people are taking four grams a day and that's kind of considered the safe dose, the max safe dose you can use. Isn't that much of a stretch to consider that somebody could take 30 grams pretty easily if they were trying to hurt themselves with a poisoning, or intentional or unintentional? They note that if you know the patient is ingested at least 30 grams of acetaminophen, that they should be considered high risk and they should be looked at at the high risk line on the Rm nomogram. Who modified algorithm? They also again note that this doesn't really count for things like extended release preparations or like that, but they note that those patients require special monitoring and that they're not.

Speaker 2:

They should be monitored much more frequently, especially with laboratory monitoring. They also touch on chronic overdoses, which I've seen a few times in my career. Or someone isn't taking a whole bunch, but basically is taking six grams or eight grams a day of acetaminophen instead of the four grams a day that is recommended. I have seen a couple of acute liver injuries because of that. So I mean for the pharmacist out there who sometimes think, when I'm warning patients about four grams a day of Tylenol, and is that really real? It is absolutely real and the guidelines point that out. They note that in someone who is taking their sub-super therapeutic doses but it isn't an acute ingestion that obviously acetaminophen concentrations are not going to be the same as you'd expect for an acute ingestion. So again, the Rm Matthew nomogram would basically be useless in a case like that. So they note that in chronic overdoses that if the acetaminophen concentration is greater than 20 or LFTs, the transaminase levels are abnormal. Basically you should go ahead and start an acetylcystine in those patients. So a little bit different for patients who take chronic as opposed to acute, and I've had that discussion a few times with some of my intensivists because they're like well, but this isn't really set up for an acute ingestion and there is actually some case series. There's actually some laboratory data that suggests, even for chronic congestions, that acetylcystine can be beneficial. If not so much from blocking the production of the NAQ toxin metabolite of Tylenol, that is, antioxidant properties may actually protect the liver as well, they note. On pregnancy, I am fortunate that if I have had a pregnant lady who's poisoned herself on acetaminophen I don't remember it, maybe I haven't in years past but they basically just say that the treatment is the same, except that some clinicians prefer intravenous and acetylcystine.

Speaker 2:

Considering that most places now have switched intravenous and acetylcystine, that's not that big of a change. So the other thing that they do go into some depth about is oral versus intravenous and acetylcystine. It's important to note that there is no study suggesting or case series or even in-betrothat if that suggests that intravenous and acetylcystine is any better than oral. It's, just, as many of you know, much better tolerated. If you've ever had to be in a room where they were mixing up oral and acetylcystine, you'll quickly go yeah, not having to smell that stuff or drink. It would make a lot of sense. So that's why I think most places have gone to the intravenous formulation. It's generic now and the prices come a way way down from when it first came out.

Speaker 2:

So they note that intravenous and acetylcystine is usually what is done, but they don't necessarily take a recommendation of that versus oral. They do note also that in very large ingestions that enhanced elimination should be considered, particularly with a hemodialysis, which I don't think I have seen. So they note that hemodialysis is recommended in addition to treatment with intercellulocystine if the concentration is in the oh my God level which they notice, 900. And again, I can't remember seeing anything that high, or it's associated with acidosis or altered consciousness, again with evidence of mitochondrial toxicity. They also note that if, if a hand elimination is used, that you want to use high dose anesthetial cysteine, so at least 12.5 milligrams per kilogram per hour during hemodialysis, because the dose requires some adjustment there.

Speaker 2:

So then the guidelines go into some detail about you know the starting and stopping rules and you can kind of boil a lot of the starting rules down to when in doubt treat, which is what I've been saying for many, many years. If there's any doubt in your mind the patient may have a sedaminophen toxicity, just go ahead and start therapy, but always start to stop therapy if the rules or evidence suggests otherwise. But you know, the bottom line is that it's inexpensive, it's pretty safe, even the intravenous formulation. And the trade-off is that you know if you gave them a drug that's relatively safe, relatively inexpensive, that if you're not going to miss an unintended or unneeded sedaminophen is acceptable compared to maybe not treating when you really needed to, because again, if you don't treat them, they very well may die from that or require a transplant.

Speaker 2:

So they then go into some nice algorithms and again, I encourage especially the emergency room and ICU clinicians listening to this that you know go to the guidelines and really really check them out, because I think they do a very nice job of kind of once and for all kind of going into when do I start, when do I stop, which is something that you know we've talked about a lot. But now you have, I think, something to kind of hang your hat on as far as official guidelines, as far as the decision rules about starting. That it's a kind of a nice algorithm that basically says that you know, if you know when somebody ingested a sedaminophen, if it's been within four hours, you can consider a single dose activated charcoal. I know the use of activated charcoal is pretty center dependent. Where I've worked in other hospitals it was pretty commonly given. I haven't seen a ton of that and I'll be interested in hearing what Dr Meyer says down in the emergency room. I haven't seen a ton of it used here at Methodist. We occasionally do, but not very commonly so. But they know that that especially in high dose ingestions that even within four hours there's probably a significant amount of drug left in the GI tract, you might be able to bind some of it and then, if you have a level. If they hit the emergency room within zero to four hours, you just get an acetaminophen concentration, and that's true if it's up to eight hours as well. If it's past eight hours, you not only get an acetaminophen concentration but also a comprehensive metabolic panel. So look for LFTs, obviously, and if it's more than 24 hours, the basically the same thing.

Speaker 2:

If the patient has an ingestion greater than 30 grams or you're unsure, they basically say just go ahead and start treatment and then, if the then, once you get a level back and you know when they took it, you can plot the level on the NamaGram, the modified room and MathuNamaGram. If it's below the treatment line, you can withhold an acetylcystine and just monitor the patient. If it's above the treatment line, then you want to obviously continue an acetylcystine, and if it's above the high risk line, you want to see, you want to take a look and monitor LFTs closely. And those are the patients that might require a hemodialysis or also permittal, which in fact the guidelines don't touch on but has been studied now in the last several years as a potential adjunct to an acetylcystine. So that's worth noting as well.

Speaker 2:

I in my world I rarely know exactly when patients took it. They either can't tell me or don't want to tell me so often. If the history is unreliable or unknown, the guidelines say then just go ahead and get an acetylminifin concentration and a comprehensive metabolic panel. If the level is greater than 10 or the AAC and ALT are abnormal, they basically get an entire treatment course of an acetylcystine. If the acetylminifin concentration is less than 10 and the LFTs are normal, you can actually withhold an acetylcystine. So again, that's some pretty hard and fast rules that I don't think existed before and I think will really help appropriate use of NAC and making sure that patients don't get it if they don't necessarily need to get it.

Speaker 2:

They do go into some detail after that and talk about the administration of inocidal cysteine. Most hospitals have gone to the so-called two-bag regimen. That makes it a little easier to give, but the guidelines themselves basically say that you want to just go ahead and start with a loading dose if possible, and then again the so-called two-bag method of giving the rest of the dose over 24 hours. They note that if the patient has a sedimental concentration of less than 10 and INR of less than 2 transaminases that are normal and the patient is clinically well after that two-bag infusion you can go ahead and stop any sedal cysteine. However, they say that if that patient has any abnormal LFTs or doesn't look clinically well, you want to continue in a sedal cysteine. And that's something that I know. I've recommended many times over the years that if LFTs are going up or the patient has lactic acidosis you want to go ahead and continue in a sedal cysteine past that first treatment course and the guidelines even note that they even give a dose at 6.25 milligrams per kilogram per hour and then keep trying to sedimental levels and ASD and ALTs and INRs every 12 to 24 hours and then, once all those criteria are met that we've talked about before, you can go ahead and stop in a sedal cysteine. Again, some pretty nice and fairly straightforward recommendations about when or when not to start in a sedal cysteine doses, when to stop things along those lines. So again, if you get a chance to read those, I think they're excellent and really kind of for once, give us some pretty straightforward ways to look at that.

Speaker 2:

As I mentioned before, they didn't really talk about famypazole for high-risk sediment aminophenoverdoses. We all know famypazole, of course, is indicated for the treatment of toxic alcohol ingestions, primarily ethylene propylene glycol and it's because it's a competitor inhibitor of ADH and it's been actually I didn't realize it's been around since 1997. I did a little research on this Again. It just makes me feel old because I remember when it very, very first came out. Why it might work for acetaminophen toxicity is because it's a potent inhibitor of cytochrome P452E1, which is one of the pathways by which the toxin, the tabloid of acetaminophen, is produced. And so there was some in vitro studies looking at its ability to basically decrease the NAPQI toxin metabolite of acetaminophen and found that it did. In vitro studies did decrease the production of that, again by inhibition of cytochrome P452E1.

Speaker 2:

Then several case reports and when case series and high dose ingestions basically found that hepatopoxicity quickly improved, so like LTEs immediately started to come down, abgs were improved because lactic acidosis was resolving and things like that, the case series itself actually looked at 35 cases and found only one death. And these were all high risk patients with high, high doses ingestions who were receiving anesthetical cysteine. And then there was an interesting, a healthy volunteer study I'm not sure how they got the volunteers for this who got a single non-toxic dose of acetaminophen and then they measured toxin metabolite levels of acetaminophen and they randomized patients to either placebo or getting plamipazole. Now again, it wasn't like they took 10 grams of acetaminophen, but they took about four grams of acetaminophen and then measured the production of the toxin metabolite and they found that in the patients who received famipazole that toxin metabolite production dropped dramatically. So it is certainly reasonable to consider famipazole.

Speaker 2:

Again, I wouldn't use it in everybody, but with high dose ingestions or in patients whose LFTs are getting worse and worse or they have evidence of mitochondrial dysfunction, it's probably reasonable to add famipazole with anesthetical cysteine. Some have argued that you could use it in place of. I certainly wouldn't do that. Again, there's not very few reasons why people couldn't tolerate anesthetical cysteine. I have seen a couple cases of anaphylactoid type reaction centravenous anesthetical cysteine. But in those patients you could go to oral and they may not like it, but it's going to work.

Speaker 2:

Finally, I did want to touch on and again the guidelines don't really talk about this the King's College criteria. This is the criteria that's been used for years now to determine whether patients should be referred to a transplant center. So again, if you're not in a place where you're a transplant center and we don't deliver transplants at my hospital, keeping an eye on this is as you're assessing the patient. The King's College criteria does predict a poor prognosis and again, that's why, if it's high enough, they should immediately go to a liver transplant center for adjustment.

Speaker 2:

It looks at several factors. Interestingly, only a couple of them are LFTs, for example. They looked at hepatic encephalopathy development. They look at metabolic acidosis production and they also look at serum cratinine and they note that if your scores are high enough, it predicts about 77% of the total depth associated with it. So again, the calculation tool is freely available on the internet and if you have a patient who's again had prolonged anesthetal cysteine therapy or has a high risk ingestion and finalities are still going up and the patient's starting to develop metabolic encephalopathy or hepatic encephalopathy as well as a high INR and a high cratinine, you really should consider early referral to a transplant center. They note that just because you don't score high enough on the King's College criteria doesn't necessarily mean they absolutely don't need referral. It's just it's a specific but not sensitive criteria. So that's something to keep in mind.

Speaker 2:

So a lot of information, but I think the guidelines have done a really good job of codifying how to use anesthetal cysteine in acetaminophen overdoses, which again we've done for you know probably 60, 70 years now. But having some way of kind of systematically doing that and then talking about some of the other stuff as well, as now with some information. Looking at Femipazol, where does that kind of fit in the guidelines? Don't talk about that, but that's something to think about. So that's kind of my take on all this. But I am not an emergency room specialist. I've never pretended to be again. Fortunately, I have our guest star, dr Kayla Myers, and she's going to give us her perspective on all this right after this message from CE Impact.

Speaker 1:

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Speaker 2:

So we are back talking about the brand new American and Canadian guidelines for acetaminophen overdose that were just recently published in JAMA. And, as I mentioned earlier, I am grateful to Dr Myers, who's joining us. He could give us kind of her perspective. Dr Myers is an experienced and emergency room clinical specialist and they're the ones to see these patients almost always first. So again, kayla, thanks again for joining us. What are, what's your take on these guidelines? What are some pros, cons, and where do you see them fitting into your practice?

Speaker 3:

Thanks, dr Wall, and I appreciate you having me on today's podcast.

Speaker 3:

As you mentioned before, you know toxicology and with our poisonings we don't really have robust literature out there and a randomized controlled trials, and a lot of what we use to dictate our therapy or recommendations are from case series and case reports, and so now we finally have like this consensus recommendation in like actual guideline on an overdose that we've had for many, many years, as you had noted before.

Speaker 3:

One of the pros I would like to point out here is, yeah, it gives us like solid direction of when to treat and when not to treat. I think the nomogram as you mentioned, I like to show my students, residents as well, but in the ER often we don't know when they overdose or what time they ingested, and so it can't really be applied to our patients that come through the ER. So I do think it gets like very much black and white of yes tree or here you can hold off where sometimes before it's like well, their levels, this we think maybe ingested this, let's hold off and repeat the title level and four to six hours and then, if it's a elevated start neck then so it's going to be a bit more fuzzy before them, but now we have some clear cut direction of hey, no use to start neck and when not to start neck.

Speaker 3:

I also think it's really helpful. So, granted, we start the neck and the ER and I don't often see the patients, you know, after they get admitted but I think it's also helpful where they give solid, you know concrete directions of continue neck until this happens, versus you know well, once you got the 24 hour you can stop the neck. I think sometimes that gets confusing from your nursing as well as providers that oh no, it's been the 21 hours we can stop the neck, versus teaser Still, this can we, can we stop it now? So I think that's really helpful and I think that's awesome that we have some now black and white direction in terms of when to start, when not to start.

Speaker 3:

One of the limitations and you kind of noted this earlier to is the dosing. So if you look, they have here mentioned in this the trial or the this consensus here that they had over 15 variable dosing strategies for Ivy neck. So it's only FDA approved for the three bag method. But if you look out there there's a various dosing for two bags for one bag, and so really you can kind of pick your poison on what you want to do and no pun intended yeah.

Speaker 3:

Pick your dosing you know method and just continue the neck until your you know LFTs improve and your I and R improves and patients over well improving. But there's so many different dosing strategies out there that it might have been helpful to have some clear cut, as this has been the most studied, or this is what you know most case reports have found and this is what they found to be the most effective.

Speaker 3:

You know they do highlight that at least 300 mgs per kilo is recommended, which would also fall default to the standard three bag method. But I think having some more direction on the dosing regimen would would have been helpful in this consensus guideline. The other thing I wanted to note, and as you mentioned to Dr Well earlier, is the title, initial time and a level. I think sometimes it's well if it's, you know, greater than 50 or greater than 20 to 50, let's go ahead and start neck in here. They have no if it's greater than 10 at any point in time, especially if we have an incredible history or we don't know the time of ingestion, give the neck knock is very little side effects for the most part is pretty well tolerable. So when in doubt, just give, as you had noted earlier. So I think that's also great that they have noted that here and highlighted that as well for our users.

Speaker 2:

And again, this might just be the old man to be talking, which usually is. You know, I when's the last time you was as an emergency room expert saw oral anesthetical system given yet no. You've never seen a given on.

Speaker 3:

Yeah, I can't speak to oral. I know it has a bad odor, just from what I've learned in my training, but I can't say that it ever.

Speaker 2:

And I'm not surprised by that kale. I mean, you know, again, you know when it, when it first came out, I remember and again it's kind of terrifying to me that how old all this stuff is. But you know, when it first came out it was, as you might imagine, unbelievably expensive and so, like every hospital, I, you know, friends of mine, worked out hospitals and this really kind of defined right, you know, the only people who got IV neck people who couldn't tolerate the oral, blah, blah, blah, blah, blah, you know. And now, of course it's, it's generic and and pretty expensive, and I think, I think, clinicians are, as you pointed out, you know, they're pretty comfortable using it, that are pretty comfortable knowing the dose, and even though there's 87 different, you know, dosing regiments out there, you know you use the one your hospital uses and you get used to using it.

Speaker 2:

I, you know it. If, if some of the more more veteran listeners you know have probably, you know, seen or smelled it, yeah there, there ain't no escaping it, you know it would stink up the entire emergency room and so you might imagine everybody hated it and and and. So you know, I think that you know that is is one good thing is that you know we don't have to subject not only the patient but every you know personnel on the emergency room and that's why that passes by the nurses. You know a staging going on. My God, what is going on over here? I think that really helps. I've seen a couple of cases where, again, it's the patient who took six grams a day.

Speaker 2:

I hurt my back and I just kept taking Tylenol because it kept working and it's like, did you not read that you're not supposed to take more than four grams a day? And of course patients don't know how much is in it, they don't know all that sort of stuff. I've seen at least two cases of that over the years and I unfortunately saw a guy who had a bad sinus infection and was taking, you know, a pseudo-fed with Tylenol and of course you know it wasn't the pseudo-fed. They got him into trouble, it was popping these things like candy and then he got into real trouble with the acetaminophen. So, and in all those cases we did give you know, anesthetial cysteine, even though the levels were, you know, undetectable, because you know he had taken his last dose 12 hours ago or whatever.

Speaker 2:

So it was nice that I think these guidelines really did, you know, finally kind of clear up what I think most people have done for a long time. But again, there was no real codification of it. So I was kind of glad to see that. So in your experience, dr Myers, what you know, what it says to check the CMP and check the acetaminophen level, you know in your experience, you know, is happy if you found that that's easy to you know it's easy to get that done. I mean, you know, have you gotten Tylenol levels back in a timely manner? I mean, you know again, we work in a pretty large tertiary care hospital but maybe in other places you've worked out, has that been a challenge to kind of get on time?

Speaker 3:

Yeah, here at Methodist I will say, like our medics are pretty good If they are bringing in like an overdose and there's bottles or anything around where the patient might be, they're pretty good at grabbing it and bringing it in.

Speaker 3:

And in that case like it's great, because then, even if you know it's not what they adjusted, we can at least gauge an idea of like how much they took, and then we don't necessarily have to wait for that Tylenol level to come back. It's like, hey, this bottle's empty. Hey, this is what we calculated based off this weight. But we should just empirically start Right In the cases that we don't which we know we do have those as well are, I would say, pretty good. Here at Methodist I'm getting our Tylenol levels back routinely. But I will say there are sometimes too where, like, if we know that the ingestion is likely high or the dose is going to be high, sometimes we just don't even wait, sometimes we just empirically start and then once we get that Tylenol level back and it's, you know, less than 10 or what have you, then we can stop.

Speaker 2:

Well, it sounds like you guys have been following the guidelines before they even came out. So again, that's as current as exactly they say to do. So that's good to hear. So, and I guess, finally, I was going to touch base on Femipazole. Again, I have not had a chance to try Femipazole in acetaminophen overdoses. I have read a couple of blurbs about it, you know, as you point out in the toxicology literature. You know, sometimes the best thing you have to go off of is a couple of case reports. But I have not had a chance to use this. I don't know if you have or what your thoughts on Femipazole use and high ingestion acetaminophen overdoses is.

Speaker 3:

Yeah, I fortunately have not encountered using Femipazole in Tylenol overdoses. I think mechanistically it makes sense. I think it's there, but as you mentioned like just the case reports and case series and stuff like that, it would I need to look more into it. I would agree with you, though that in that I don't think there it should replace NAC, like ROTO works for Tylenol overdoses. Mechanistically it's a safe drug. It's relative like side effect profile is low, it's not very expensive. There's just too many benefits of NAC that we know of in Tylenol overdoses for Femipazole to replace it as a potential adjunct. I think there's opportunity there, but in terms of replacing it I would not agree with that.

Speaker 2:

Yeah, I totally agree with you. And it's funny because Femipazole is kind of, from a pharmacological perspective, kind of like NAC, right I mean it's. The price has gone way down, so it's pretty affordable now. It has virtually fewer, no side effects. People tolerate it really well and I've used it for toxic alcohol ingestions. The biggest pain in the butt was having to adjust the dose when they were getting to common dialysis. So it's kind of funny how they kind of parallel each other and so it's like if you had somebody who is basically getting worse and worse LLT's are rising. They've got lactic acid doses. They're getting goofy on you. It's like the go-no-go decision on Femipazole will be about the same as NAC. It's like well, can't hurt them, it's dirt cheap, let's give it a shot. There's at least some evidence to suggest it might work. So why not give it a shot and see what happens, especially when the alternative is sending these patients to a transplant center? So yeah, so that's good. Any last thoughts you have for us?

Speaker 3:

No, I think this is great. I think it's a great starting point for the toxicology world with finally having a census guideline report for at least one of our most common and oldest overdoses. So I'm glad we got something out there.

Speaker 2:

Yeah, me too, and something that again, most years I get a little song and dance to our interns or our ones about acetaminophen overdoses and overdoses in general. So I'll probably have to kind of overhaul it. But I'm glad, like you, I'm glad that there is at least something to point to, whereas in years past, yeah, everyone agreed it was a huge NAC, but how you used it, why you used it, et cetera, et cetera, was all kind of up in the air. So, yeah, I'm glad that somebody finally came down on the side of saying this is what we think you should do. So, dr Myers, thank you so much for joining us Again. We appreciate your insight. Hope you don't mind if I call on you again if we have another emergency room type topic. We do do some of those. We don't do all this ambulatory care. So, yeah, I might be calling on you again and we again appreciate your expertise and your time.

Speaker 3:

Absolutely. Thanks so much for having me. I appreciate it.

Speaker 2:

No problem, that's it for this week of Game Changers. Again, thanks for listening to us. Time flies. I don't know where it's going, but the most important day is today. We'll see you next week.

Speaker 1:

Jen here. Be sure to check out our education at cempackcom. You'll find it to be your one-stop shop for all the CE resources you need. Become a pharmacist by design member today to access it all for free, including CE for this podcast. Thanks for listening. We'll talk to you next week on Game Changers Clinical Conversations.

Clinical Conversations on Acetaminophen Overdose Guidelines
Guidelines for Acetaminophen Poisoning Treatment
Guidelines for Acetaminophen Overdose in US/Canada
Femipazole vs NAC for Acetaminophen Overdoses