[SPEAKER_01]: Hello and welcome back to Agrax, I'm Jeff Wolpa and I am thrilled to have a fabulous show for you today.
[SPEAKER_01]: I have with me Dr. Tyler Jones and we are going to talk about the two really interesting topics of SGLT, two inhibitors and GLP-1 receptor agonist, kind of the myths and truths about those and Tyler is a fabulous guest.
[SPEAKER_01]: So he works at Kaiser Permanente in Los Angeles.
[SPEAKER_01]: he teaches the RNA students there and he recently became more certified in obesity medicine which is really fascinating and maybe he'll tell us a little bit about that and he's going to split his practice between that and anesthesia.
[SPEAKER_01]: He doesn't have any disclosures but he does have this really fabulous blog called anesthesia thoughts.
[SPEAKER_01]: He talks about kind of and Tyler let you tell us a little more, but really interesting things that maybe people have misconceptions about or that are maybe a little Practice not in the way the evidence might suggest and so that I find it really interesting and really really worth a visit to his blog And then we're gonna talk about two of those things today.
[SPEAKER_01]: So Tyler welcome to the show Thank you, Chad Tell me a little bit about how you got started with the blog and a few little thoughts
[SPEAKER_00]: And one kind of passion for education, for myself and for other people and keeping up on the literature is pretty difficult because they're more studies published every month than any one of us can read and quite frankly, most of these articles that come out are not super relevant to the day-to-day practice of anesthesia.
[SPEAKER_00]: It's really important to do a lot of investigation into smaller things like how anesthesia works, but
[SPEAKER_00]: to try to sit between articles like that and an article about a new pain medication that I could use every day.
[SPEAKER_00]: My practice is difficult.
[SPEAKER_00]: So part of my impetus to start blog was to try to sit through that noise myself and then bring papers that every day anesthesiologists can use every day.
[SPEAKER_01]: Yeah, fabulous.
[SPEAKER_01]: I think that is one of the things I've noticed about your blog that I really like is that it is absolutely something that I think any anesthesiologist no matter what they're kind of background and taking through the literature is they can really get a lot out of it.
[SPEAKER_01]: So I think you're doing a fabulous job there.
[SPEAKER_01]: Tell me a little bit about the decision to do this board certification and obesity medicine.
[SPEAKER_01]: That's not I don't know that I've seen that before.
[SPEAKER_01]: What was that process and what made you do it?
[SPEAKER_00]: And right now the process is you can either do a one-year fellowship and take the exam or you can go through a CME pathway where you have to do certain accredited courses of 60 CME hours and then take the exam both results and you're being board certified.
[SPEAKER_00]: By desire to do this was sent from I have a big interest in providing medicine and
[SPEAKER_00]: I've spent a lot of time reading about that through the recent years, so this, to me, was a way to branch out and be able to split my practice, to do a little more of that in an obesity medicine, it's not necessarily strictly preventing medicine, but to get into that field and give myself a little more variety, as opposed to just being an operating room every single day for estimate career.
[SPEAKER_01]: very cool.
[SPEAKER_01]: All right.
[SPEAKER_01]: Well, that's awesome.
[SPEAKER_01]: And I'm sure people can look into that if they're interested in learning more about it.
[SPEAKER_01]: So let's talk about these two really interesting topics.
[SPEAKER_01]: Let's start with STLT2 inhibitors.
[SPEAKER_01]: So tell me a little bit about what they are, but just maybe even to spell out that acronym just for people who don't know what it means and then how they work.
[SPEAKER_00]: Yeah, so that's due to inhibitors are class drugs that originally were for treating diabetes.
[SPEAKER_00]: They caused the kidneys to resort less glucose and now they're being prescribed for bolt woundocations or cardiac patients with heart failure and for patients with chronic kidney disease.
[SPEAKER_00]: And occasionally they're even used off-labeled for weight loss of the
[SPEAKER_00]: lot of patients are being put on them.
[SPEAKER_00]: Though, because of the mechanism of action, they lead to lower insulin and then higher gluten done, which promotes ketogenesis.
[SPEAKER_00]: So insulin getting a little under the biochemistry, higher levels of insulin act as a negative feedback to inhibit ketogenesis.
[SPEAKER_00]: And the problem with these drugs is by having lower levels, you have an increased risk of developing ketones.
[SPEAKER_00]: Pretty clear in the literature that patients taking these have a higher risk of QS sedosis.
[SPEAKER_00]: And that can be from the number of factors.
[SPEAKER_00]: Typically, if people are just living their day-to-day lives, that risk has been able to put the risk increases when people have these acute stressors such as an infection, if they're fasting for some reason, if they have surgery.
[SPEAKER_00]: And this is where the concern comes on our end
[SPEAKER_00]: do these medications in Prusa risk of Q2S doses during surgery.
[SPEAKER_01]: And I think that the teaching, right?
[SPEAKER_01]: I mean, certainly what a lot of people are told and believe right now is that they absolutely do, that these people on these medicines are much more likely to have, you glycemic DKA during the perioperative period, right?
[SPEAKER_01]: I mean, that's kind of what people believe.
[SPEAKER_00]: Yeah, so I think we should just clarify some terminology.
[SPEAKER_00]: These medications definitely increase the risk of ketoacidosis.
[SPEAKER_00]: Whether that is eucalyseemic or diabetic ketoacidosis is a little bit just about definitions.
[SPEAKER_00]: If someone goes to the above 200 in their diabetic, then we would define that as diabetic ketoacidosis.
[SPEAKER_00]: But because a lot of people are taking these, not for diabetes, they may have you placing it either way.
[SPEAKER_00]: It's a little bit of a semantic approach because QS doses, as QS doses, whether or not the sugar is high and it's still going to be harmful.
[SPEAKER_00]: We've had multiple studies now and some meta-analysis showing that these do have a higher instance of QS doses just in the general population.
[SPEAKER_00]: The FDA came out a few years ago and recommended that we hold these medications for three to four days before surgery, due to a concern of surgery promoting the QS doses from these.
[SPEAKER_00]: And I think that was a good recommendation.
[SPEAKER_00]: At the time, we didn't have some of the studies that we now do.
[SPEAKER_00]: So it's always good to operate out of the abundance of caution until we have more evidence.
[SPEAKER_01]: Yeah, I mean, I think that's absolutely right.
[SPEAKER_01]: So you've defined these two things, right, that essentially are the same.
[SPEAKER_01]: I think that one of the tricky things about USMDK is that our typical way of being concerned that someone might be in DK is that they have a high glucose level.
[SPEAKER_01]: So if, in fact, they do not, then we may not think about it.
[SPEAKER_01]: So important to think about it.
[SPEAKER_01]: And do we know?
[SPEAKER_01]: So the important, so you've answered the question, do these drugs make you more at risk or decay?
[SPEAKER_01]: Yes.
[SPEAKER_01]: Do does it matter whether you, I guess the big question is, does it matter whether you hold the medication or not before surgery because that's really, we're not going to refuse to do surgery on someone who's ever been on one of these.
[SPEAKER_01]: So the question is, how do we handle people coming in for surgery who are prescribed these medications?
[SPEAKER_00]: Right.
[SPEAKER_00]: So that's the big question.
[SPEAKER_00]: And there are a few papers that have come out.
[SPEAKER_00]: They are all retrospective studies.
[SPEAKER_00]: So we don't have randomized controlled trials at moment to show us whether we have an increased risk from taking these medications or holding them before surgery.
[SPEAKER_00]: But looking at this retrospective data, we start to see that maybe the concern about.
[SPEAKER_00]: diabetic or replacing ketosis with surgery is not as big of a concern as we once thought.
[SPEAKER_00]: And we also have some signals that there could even be benefits and continuing these medications.
[SPEAKER_00]: So I'm going to get into one of these studies.
[SPEAKER_00]: This is a retrospective study.
[SPEAKER_00]: And the authors looked at patients who had diabetes, were taking S22 inhibitors, and were undergoing one of several emergency surgeries.
[SPEAKER_00]: The emergency surgery is because this is a retrospective study, they wanted to assume that patients were probably still taking these medications, as opposed to elective surgery, but they've been meld.
[SPEAKER_00]: So given this a retrospective study, we have plenty of limitations, one way that the authors tried to control for the patients taking STD2 inhibitors, as they made sure that they had a pharmacy refill within a certain amount of time, that they could still have doses left when they were admitted in undergone surgery.
[SPEAKER_00]: What they found was a 3.8% increase in the incidence of diabetic ketosvosis in the SJ2 and Hibbert group, and a 3.5% in the match controls.
[SPEAKER_00]: So there's no statistically significant difference between those groups.
[SPEAKER_00]: So they get some point.
[SPEAKER_01]: So, yeah, just to clarify, so in this retrospective study,
[SPEAKER_01]: They did not find any difference between the people who they, as far as they could tell, we're taking STL-T2s and those who didn't.
[SPEAKER_01]: Exactly.
[SPEAKER_01]: Okay.
[SPEAKER_00]: Now, when we're talking about the definitions, these authors looked at using IC-10 codes for both diabetic Ketoacidosis and Acidosis.
[SPEAKER_00]: Unfortunately, there's no IC-10 code for you glycemic Ketoacidosis.
[SPEAKER_00]: So that limits the ability to do some of these studies.
[SPEAKER_00]: Now, because they looked at both diabetic utoscosis and the acidosis, there is a concern that they were capturing patients who may not have been in QS doses.
[SPEAKER_00]: In the sensitivity analysis, they excluded just the regular acidosis, ICB-10 code, and found no difference in their results.
[SPEAKER_00]: So I think this is a pretty well done retrospective study showing that there was no major difference between the instance, between groups.
[SPEAKER_01]: this suggests that actually, these medications, at least in this study, did not cause an increased risk of decay.
[SPEAKER_00]: Yeah, that's what this is suggesting.
[SPEAKER_01]: Okay, and this was not about whether they held it or not.
[SPEAKER_01]: This was just about, if they thought they were on it, did it matter.
[SPEAKER_00]: Right, right, this is, it seems fairly pragmatic because it's limited to emergency surgeries.
[SPEAKER_00]: But again, we don't know that crystal parabens, we'd love to have an RCT knowing that patients either did or didn't take the medications.
[SPEAKER_00]: Okay, what else do we know?
[SPEAKER_00]: So we have a couple other studies looking at this.
[SPEAKER_00]: I think what is important, what is interesting for me to highlight because this is sort of study that I see all the time and it gives you some evidence and I think people may read it and think a certain file.
[SPEAKER_00]: But when you delve deeper into the study details, I think it's not as clear as one may help.
[SPEAKER_00]: So this is another retrospective study.
[SPEAKER_00]: Interestingly enough, published in the same journal in the same month as the one I was just describing.
[SPEAKER_00]: And this study looked at patients taking STT2 inhibitors and compared into controls similarly.
[SPEAKER_00]: But their primary outcome was defined differently.
[SPEAKER_00]: So their primary outcome was defined
[SPEAKER_00]: defined by certain lab values of base access or by carbonate and having a glucose less than 200 and a lactate less than 3 millivolts.
[SPEAKER_00]: This study did not restrict their results to a D.K.A.
[SPEAKER_00]: code and they weren't measuring key tones.
[SPEAKER_00]: So immediately my concern with this is that we may be over capturing patients rather than just
[SPEAKER_00]: So what this study found is they showed an increased incidence of acidosis in the patient-stating STO-D2 inhibitors.
[SPEAKER_00]: However, when you look at the incidence, the overall incidence was about 30% in the STO-T2 group and 28% in the controls.
[SPEAKER_00]: So it's a huge difference compared to that prior study that found the incidence was around
[SPEAKER_00]: So again, my thought goes to a concern that they may be significantly overcatching this event because it was not nearly defined enough in the primary outcome.
[SPEAKER_01]: Right.
[SPEAKER_01]: So they may have been, they probably must have been capturing other acidosis that were not diabetic keto acidosis because it's really hard to believe that one third of both the patients and the controls were getting decay.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: And when they restrict their results to just emergency surgeries, UCO's numbers go up to 46% in the SJ2 group and 42% in controls.
[SPEAKER_00]: So again, I love having more information, but this is study where I have enough concerns about the methodology that I'm not really sure what to do with this data.
[SPEAKER_01]: Yeah, since fair.
[SPEAKER_01]: Okay.
[SPEAKER_01]: So that study may be less helpful.
[SPEAKER_00]: maybe less helpful.
[SPEAKER_00]: And this is the thing, research is not easy to do, and if I was good, I'm not someone who does primary research myself, but if I was giving anyone advice, I would say, try to be very clear with your primary outcomes, so that we get useful data, because having data that is confusing can
[SPEAKER_00]: be almost more confusing to everyone than not having done the study in the first place.
[SPEAKER_01]: Right.
[SPEAKER_01]: Yes.
[SPEAKER_01]: I agree with that.
[SPEAKER_01]: And you know, it's right.
[SPEAKER_01]: When you look closely and you think 30 percent, you know, that, and you know, there's no way one out of every three patients.
[SPEAKER_01]: who is not even on these medicines is getting decay then that it's but if you just quickly look and you see the abstract and it just says oh there's a higher risk of acidosis you know that you draw different conclusions so I agree with you it's you have to be careful with the study because people might just very quickly look at it and draw conclusions from that.
[SPEAKER_00]: right, right.
[SPEAKER_00]: So there's one more paper that I think is interesting with these Astro-D2 inhibitors, and this is a paper looking at patients who are undergoing
[SPEAKER_00]: cardiopulmonary bypass surgery.
[SPEAKER_00]: Now, these patients, they did have the dose the day before surgery, but they did not have the dose the morning of surgery.
[SPEAKER_00]: Again, this is a retrospective study looking at the outcomes between these patients.
[SPEAKER_00]: And note to believe this study was not looking at the incidence of QS doses in either group.
[SPEAKER_00]: What they were looking at was seeing that there was a
[SPEAKER_00]: a composite outcome of cardiac events in the patient's taking estates to connectors.
[SPEAKER_00]: We know these medications in a chronic timeline have a protective effect on the heart, and that's why they're prescribed for a lot of patients with heart failure.
[SPEAKER_00]: So they wanted to see if there was an acute protection with these medications.
[SPEAKER_00]: Patients did have them then held them warning of surgery,
[SPEAKER_00]: But we'll see, the primary outcome, it was defined as a composite of events looking at an increase in high sensitivity to high sensitivity components.
[SPEAKER_00]: They were also looking at the low cardiac output syndrome defined as required nine of tropes or 48 hours, or mechanically circulatory support.
[SPEAKER_00]: And then they also looked at the retake mortality.
[SPEAKER_00]: What they saw was that,
[SPEAKER_00]: this outcome occurred in about 27% of SJ2 and Hibbert patients compared with 42% of controls.
[SPEAKER_00]: So that's a pretty significant difference between those groups.
[SPEAKER_00]: Notably, the majority of this outcome was driven by difference in elevations in the high-sensitivity, sorry, high-sensitivity component.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: Okay.
[SPEAKER_01]: So this is really interesting.
[SPEAKER_01]: So the people who were on the SDLT2 inhibitor had quite a striking decrease in a tripon and rise after surgery.
[SPEAKER_01]: So what conclusion do we draw from that?
[SPEAKER_01]: Probably that these are protective.
[SPEAKER_01]: These are cardiovascular protective as we know.
[SPEAKER_00]: Right.
[SPEAKER_00]: So we know they have a chronic cardiovascular benefit.
[SPEAKER_00]: Maybe they also have a
[SPEAKER_00]: this is inferred by the elevations of lacquer of with proponent, myocardrongery, and there's definitely a question of how much injury is normal acceptable because I think there's this growing
[SPEAKER_00]: concern looking at mitochondrial injury after non-cardiac surgery and metering patients opponents.
[SPEAKER_00]: Some of this data, this is actually something I'd like to look into more probably right opposed on the future, but some of this data suggests that maybe even 20% of our patients going for normal surgery have an elevation to opponent.
[SPEAKER_00]: So what is clinically significant here to me is not super clear.
[SPEAKER_00]: However, I think this is worth giving us pause and saying, okay, we have some evidence that suggests holding these medications may not actually reduce ketoS doses, and now we have some evidence that suggests continuing these medications may offer some benefit.
[SPEAKER_00]: So that's what gives me pause when we are looking at updating our thoughts on this recommendation from the FDA.
[SPEAKER_01]: Yeah, what's interesting to think about, too, is as you mentioned, there may be some differences in these groups.
[SPEAKER_01]: You could imagine that the group on STLT2 inhibitors, the fact that they're on that might indicate they have better primary care or that they are, I don't know what insurance coverage is like for these, but maybe they are able to afford these out of pocket and so they have more wealth and with that they're able to have better overall healthcare.
[SPEAKER_01]: So you could imagine there might be ways in which the STLT2 inhibitor is a marker for something else that's not being measured.
[SPEAKER_00]: absolutely these drugs are still fairly expensive and we know that having a higher income is correlated with having better health outcomes.
[SPEAKER_00]: All these studies are retrospective, so plenty of confounders can be here.
[UNKNOWN]: Yeah.
[SPEAKER_00]: Another ball with this, this paper did not look at the instance of QS doses.
[SPEAKER_00]: However, we know that a lot of patients going into the ICU have very tight glycemic control, often managed with insulin infusions.
[SPEAKER_00]: And as I said, before insulin will suppress that ketogenicysis risk.
[SPEAKER_00]: So giving these patients insulin,
[SPEAKER_00]: who would have prevented it any key to as a doses?
[SPEAKER_00]: The authors didn't look at this, but it's just something to keep in mind and say, well, this subset of populations started with some sort of patients that benefited could be different because they're receiving a different level of care than maybe mitigated at any risk from continuing these medications.
[SPEAKER_01]: Yeah, absolutely.
[SPEAKER_01]: That makes a lot of sense.
[SPEAKER_00]: So, I think one thing is people might be asking, well, where do we go from here?
[SPEAKER_00]: Because we have this recommendation and what can we do about it with these medications?
[SPEAKER_00]: Should we continue them?
[SPEAKER_00]: Should we not continue them?
[SPEAKER_00]: I don't have a clear answer to that because it'd be great to have better data.
[SPEAKER_00]: Some hospital systems have developed some protocols for avoiding canceling these patients if they take the medications beforehand.
[SPEAKER_00]: So the way that a couple of these systems have done this is by measuring beta hydroxybutary, which is one of the main ketones in the blood in the pre-opsite.
[SPEAKER_00]: So patient comes in, they say they continue to medication, you don't want to cancel a surgery, you can check a serum ketone level and C. Is it elevated?
[SPEAKER_00]: Is it not?
[SPEAKER_00]: This is, we don't have randomized controlled trial data showing what to do with this,
[SPEAKER_00]: what we know about risk from other studies to say if the levels below a certain point, maybe a state to proceed with surgery.
[SPEAKER_01]: Okay, and is that cut off set at differently at different hospitals, or is there kind of a generally accepted level?
[SPEAKER_00]: Yeah, so there's one paper that looked at this and they used examples from Northwell Health System and another hospital system.
[SPEAKER_00]: They both set the levels slightly differently, but they were using cutoffs between 1.5 and 2.0 millimoles.
[SPEAKER_00]: Typically, the risk for ketoacidos is a sighted as occurring at where both three millimoles and just for reference, when people are doing a ketogenic diet, they are said to be in ketosis at 0.5 millimoles.
[SPEAKER_00]: That level of 1.5 or 2 is allowing for some ketosis, but not a significant amount.
[SPEAKER_00]: I'd say if somebody is below half a million more than the risk was probably very low, but you always want to conserve the other factors.
[SPEAKER_00]: Aces patient going to be eating after surgery is going to be the most significant factor.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: That makes sense.
[SPEAKER_01]: So if they're 1.5 to 2, they're getting higher than you probably should be just from a keto diet and therefore, you know, you may be worried that they're at higher risk for going to actual decay.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: So both of those levels definitely the concern for doing you do the search for right now or who manage your patients and then do the search
[SPEAKER_01]: Okay, so what in the end, well, so let me ask you this.
[SPEAKER_01]: Make sure I have this correct.
[SPEAKER_01]: In general, not around surgery, just in general, people on STL-C2 inhibitors do have a higher risk of decay than patients not on them, right?
[SPEAKER_01]: That we do know.
[SPEAKER_01]: Right.
[SPEAKER_01]: Okay.
[SPEAKER_01]: But there's not, sounds like there's not a lot of data on what happens periodically, and the little bit that we have that we talked about are some retrospective studies, one of which showed no increase risk, and one of which showed an increase risk of some acidosis, but that included a lot more than just.
[SPEAKER_01]: diabetic keto acidosis or even keto acidosis.
[SPEAKER_01]: So it's unclear what to make of that one.
[SPEAKER_01]: So really, we don't have a great feel for what the risk, periodically, of being on these or of holding them or not.
[SPEAKER_01]: So what should we tell patients?
[SPEAKER_01]: Do you think about whether to hold their STL-22 and have it or not?
[SPEAKER_01]: And I'm sorry, I should add that you mentioned there's a study suggesting that it may be in the immediate post-operative cardio protective to have taken it.
[SPEAKER_01]: So we have to take that to account as well.
[SPEAKER_00]: right.
[SPEAKER_00]: I think that based on our retrospective data, we have enough evidence to question the benefit of holding these.
[SPEAKER_00]: But you do say to anyone individual that they should just be fine going to have a surgery is not a good recommendation.
[SPEAKER_00]: I think that.
[SPEAKER_00]: The best thing to do before we have an RCT to show us some better information is to have hospitals, develop policies.
[SPEAKER_00]: Ideally, we could develop policies to check these keyton levels in the period so that we can avoid canceling these cases.
[SPEAKER_00]: And that could be seen as a QI measure of cost saving, we're not canceling these surgeries, we're helping these patients out.
[SPEAKER_00]: There are a few other points I think that just suggest maybe this risk is not as high as we think.
[SPEAKER_00]: by eating your decrease in the risk of being in Q2S doses.
[SPEAKER_00]: And many places now, including place, I work, or telling patients to have a carbohydrate beverage two hours before surgery.
[SPEAKER_00]: So that right there is going to decrease the risk of them being in ketosis if they drank their eight ounces of apple juice.
[SPEAKER_00]: And then, most of these patients are eating after surgery.
[SPEAKER_00]: You know, with many surgeries, patients are eating after I would say, depending on what it is.
[SPEAKER_00]: So you can keep that in mind.
[SPEAKER_00]: So if you have those factors working toward you, then again, maybe the risk of keto as doses is not as high.
[SPEAKER_00]: But what exactly we need to do with this information should be dependent on the hospital, you develop the policy within your group that says, we still recommend holding these based on the FDA recommendation, but it patients forgot to hold it.
[SPEAKER_00]: We have this protocol that lets us kind of rescue that.
[SPEAKER_01]: Yeah, I think that makes a lot of sense and you know, we also, I, the where I've seen it, and this is a function of the fact that I work in the ICU, but is patients who are having major surgery and they're not going to get, they're not going to eat or have any nutrition for a while post-op they go to the ICU, they're still intubated, right?
[SPEAKER_01]: Those are the patients who I would think might be at higher risk because they have nothing, they're not getting surgery, not getting it.
[SPEAKER_01]: So, you know, maybe we have to be more careful with those patients as opposed to the patient who's going to start eating a few hours after surgery.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: If you stop eating, most people are going to go into ketosis within one to two days, no matter what.
[SPEAKER_00]: So being on these medications, definitely increases that risk.
[SPEAKER_00]: If you knew someone wasn't going to be eating at your surgery, I absolutely want them holding these medications.
[SPEAKER_00]: I have time.
[SPEAKER_01]: So I think what I have taken from this discussion is that we need more data.
[SPEAKER_01]: We definitely don't have a great amount of evidence to suggest that we should or shouldn't be telling patients to hold these, but in the absence of a lot of evidence and in the presence of at least some reassuring data, maybe we should not routinely be canceling cases if patients don't hold them.
[SPEAKER_01]: Maybe we select certain patients who we might want to think about that with if they're rid particularly high risk But it doesn't there's not at least a lot of evidence to suggest we should be canceling cases routinely because patients didn't hold them Stay with us.
[SPEAKER_01]: We'll be right back All right, and we're back
[SPEAKER_00]: Right.
[SPEAKER_00]: That's pretty much where I'm at with this.
[SPEAKER_00]: I think if someone shows up for their endoscopy or colonoscopy and they didn't hold the medication, well, is that risk of I'm going to cancel surgery and they're going to eat right now or I'm going to do the colonoscopy and they're going to eat 45 minutes from now, that's probably not what's going to push them into Q to S, those are not.
[SPEAKER_00]: And I think this data is pretty reassuring for that patient.
[SPEAKER_00]: The patient is getting colorectal surgery not eating that's a different story.
[SPEAKER_01]: Yeah, okay, great.
[SPEAKER_01]: So let's move to GLP1 receptor agonists.
[SPEAKER_01]: Obviously this is a really hot topic.
[SPEAKER_01]: There's so many people on these more and more now.
[SPEAKER_01]: There's a pill.
[SPEAKER_01]: So there's going to be more people on these.
[SPEAKER_01]: So how do these work?
[SPEAKER_00]: Yeah, this is such a hot topic.
[SPEAKER_00]: And, and fortunately, I'm going to be able to give you some better guidance based on the evidence with these medications.
[SPEAKER_00]: of what to do, although controversial, certainly still exists.
[SPEAKER_00]: Of course, these medications, the primary mechanism by which they work is by slowing gastric acting with the GLK1 receptor.
[SPEAKER_00]: There seem to be some other mechanisms that are a little less well-teased down because we're seeing evidence that patients who add addictions to food, for example, or alcohol or smoking, when they call on these medications,
[SPEAKER_00]: losing their cravings for those substances.
[SPEAKER_00]: So there's probably some neural mechanism that's also working to decrease food consumption patients.
[SPEAKER_00]: But overall, these work by making people feel full, so they eat less food.
[SPEAKER_00]: Because that delay gastrogrammed team, this is the biggest concern for Alzheimer's and anesthesiologists.
[SPEAKER_00]: We're one of the biggest concerns with aspiration.
[SPEAKER_00]: And we're thinking about this every single time, we induce people to whole reason we have
[SPEAKER_00]: So if these medications are increasing, you know, residual gas, they're delaying gastrogab gene.
[SPEAKER_00]: They're increasing residual gastric contents.
[SPEAKER_00]: We want to know what should we do to manage that risk?
[SPEAKER_00]: Yeah.
[SPEAKER_00]: This initially came about because there were some case studies where patients were aspirating and had increased gastric volumes.
[SPEAKER_00]: A lot of this research was done and dogs could be where it was very easy to see that these patients had residual gastric contents.
[SPEAKER_00]: So a few years ago, the ASA released their first recommendations and those have since been revised, both the ASA and the British Association have guidelines, so I'd like to go through those and just touch on what the most recent guidelines say.
[SPEAKER_00]: Great.
[SPEAKER_00]: To the ASA, the most recent guidelines, they recommend a couple different points.
[SPEAKER_00]: The first one being they give a whole bunch of.
[SPEAKER_00]: parameters by which you can potentially risk stratify these patients to say, okay, it does this person have an increased risk of having residual gastric contents, and therefore, asked for it.
[SPEAKER_00]: If a patient does not meet any of these criteria, they say that the GOP owners have protagonist may be continued in patients without elevated efforts with gastric
[SPEAKER_00]: Now, we're going to get into this in a little bit.
[SPEAKER_00]: But unfortunately, there's no way to use their criteria to decide who has an elevated risk or not.
[SPEAKER_00]: The second part of their guideline says we can give consideration using shared decision-making to consider a liquid diet for 24 hours, consider gas refaltor sound, consider rapid sequence, into the Asian.
[SPEAKER_00]: So that's the ASA guideline.
[SPEAKER_01]: And as you said, one of the big issue here, you know, I think right, and I think you mentioned is that saying you can continue them if they're not elevated risk means you have to know who's elevated risk and that's not easy to figure out.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: We'll get into this a little more, but.
[SPEAKER_00]: The only way to clearly know whether someone has residual gastric contents is to do imaging, and the most, the only really feasible way to do that is gastric ultrasound.
[SPEAKER_00]: Unfortunately, that's not widespread right now.
[SPEAKER_00]: It's a great decision point, but if I'm going to talk to the mass of anesthesiologists in this country, it's hard for me to get that as a recommendation, because it is fairly new, right?
[SPEAKER_00]: So, the British guidelines, they're similar.
[SPEAKER_00]: The big difference between the British recommendations on the ASA ones are that the British recommendations recommend continuing the GOP and one or separate witnesses.
[SPEAKER_00]: I should go back and say, the first edition of the ASA recommendation said to hold one dose of these GOP and other separate arguments before surgery with the hope that this would alleviate some of the delayed gastric FDA.
[SPEAKER_00]: So, if the British recommendations say, there's no point in holding a dose, these patients should just be continued on it.
[SPEAKER_00]: They say specifically that GI symptoms alone should not be used into term in the risk of residual gastric contents.
[SPEAKER_00]: They also recommend continuing gastric ultrasound.
[SPEAKER_00]: They also recommend using considering our SI, using pro-kinetics that may reduce the gastric contents.
[SPEAKER_00]: Meteorone, and they do not recommend a longer fasting duration.
[SPEAKER_00]: So, similar but a little different between the two iPhones.
[SPEAKER_01]: Yeah, and that's an important point, right, is that there are a couple of, if we think that these people being on these medications have slower gastric emptying, which I think that's pretty clear that they do, then the question is, do we have them stop the medication and hope therefore that they have faster gastric emptying, or do we have them fast for longer, and therefore, eventually their stomach will empty, or something else, right?
[SPEAKER_01]: But those seem
[SPEAKER_00]: Exactly.
[SPEAKER_00]: So, I'm going to paint a picture that is clearly in favor of one of those answers.
[SPEAKER_00]: Okay.
[SPEAKER_00]: So, what is the evidence shell?
[SPEAKER_00]: The evidence is very clear that holding one dose of medication does not affect the residual gastric contents.
[SPEAKER_00]: In fact, a study came out just a few weeks ago that looked at this in a very clear way.
[SPEAKER_00]: We've had quite a few studies looking at this.
[SPEAKER_00]: This one is the best one I've seen so far.
[SPEAKER_00]: I'll just briefly go through this.
[SPEAKER_00]: They use gas revolts or sound on patients who are on semi-glutide, which is also called Ozenbichan and Govi, coming in for elective surgery.
[SPEAKER_00]: And they were following the routine fasting guidelines, and they were also told to hold one dose before surgery.
[SPEAKER_00]: So they imaged all of these patients and then they matched them to controls based on the BMI and or diabetes status.
[SPEAKER_00]: medication for.
[SPEAKER_00]: They had a total of 44 patients in each group, so not a huge study, but very well done.
[SPEAKER_00]: And what they found was,
[SPEAKER_00]: 49% of the patients in the assembly group had residual gastric contents compared to 18% of the controls.
[SPEAKER_00]: Now, they broke that down further.
[SPEAKER_00]: If you were just looking at solid contents, 42% of the assembly group versus 7% of the controls.
[SPEAKER_00]: And most significantly, the median fast generation in these patients was 14 to 15 hours between the two groups.
[SPEAKER_00]: much longer than the recommended date hours and still almost half of patients had residual gastric contents.
[SPEAKER_00]: They, again, this is a small study, but they looked at different dosing regiments because it's one of the concerns and thoughts has been that patients taking higher doses, patients being only medications for a shorter amount of time,
[SPEAKER_00]: and patients taking the drugs that last long versus, for example, some of the blue tie that's dose weekly versus the pill that's dose daily, that those increased the risk of having residual gastric content, and they found no association between that.
[SPEAKER_00]: So even patients would been on these medications for up to four years, had some full stomach.
[SPEAKER_00]: What this shows is we can determine whether or not these patients have,
[SPEAKER_00]: residual gastric contents without imaging them.
[SPEAKER_00]: And that a large number of these patients will have residual gastric contents when following the eight-hour typical fasting guidelines.
[SPEAKER_00]: Now, I've heard a lot of people say, well, there's no harm in holding one dose of the medication.
[SPEAKER_00]: And to that I'd like to try to paint a picture that there is potential harm in holding these medications.
[SPEAKER_00]: I get a new reasons why I think there's no benefit to that.
[SPEAKER_00]: I think the biggest harm in holding one dose is that we give ourselves some false reassurance that these patients are safe to undergo and a seizure without our aside that or undergo mac cases without a protected area.
[SPEAKER_00]: However, there are potential patient harms.
[SPEAKER_00]: If there are only medications for their glucose control, they may have more glucose control leading up to surgery.
[SPEAKER_00]: Once patients miss two or more dose of these medications, they start to have less tolerance for the side effects.
[SPEAKER_00]: And this means that they often need to decrease to a lower dose and then titrate back up.
[SPEAKER_00]: The way these medications are typically dose, you'll start at the lowest dose in every four or more weeks, you will increase the dose incrementally.
[SPEAKER_00]: And this helps patients tolerate the side effects of the nausea,
[SPEAKER_00]: So if somebody has helped this dose for a week and then suddenly their surgery is rescheduled and now they're off it for another week and another week, this cannot real consequences to the patients, especially if they had need to go and get it now, a lower dose from the pharmacy, maybe their insurance doesn't cover it.
[SPEAKER_00]: Some paying picture of that, there are potential harm, some holdings medications, and in the setting of no benefit, I think it's really clear that.
[SPEAKER_00]: we do with these residual gastropoling, right?
[SPEAKER_01]: And the other issue, right, is that if you wanted to really get the, some of these medications that are dose weekly out of their system, you'd have to hold, you know, you'd have to hold more than one dose, right?
[SPEAKER_01]: These things have a very long half-life.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: When we're looking at some of the luteide, which is the most commonly used one, it five doses we need to be held.
[SPEAKER_00]: So we're talking five weeks if you're dose from the weekly version.
[SPEAKER_00]: I haven't seen any studies that show doing this actually.
[SPEAKER_00]: will dissolve our residual gastric contents.
[SPEAKER_00]: This is based on the pharmacologic data of the mechanistic data.
[SPEAKER_00]: So that is one potential option.
[SPEAKER_00]: But again, I want to see some evidence of that clearly is effective.
[SPEAKER_00]: And if you're doing that, these patients, if they're on a per weight loss, we know even in that short amount of time, they'll start to regain the weight.
[SPEAKER_00]: and then diabetics obviously would need another medication to be told or blood glucose.
[SPEAKER_01]: Right.
[SPEAKER_01]: Okay.
[SPEAKER_01]: So if we have a study suggesting that even after 12 to 14 hours of fasting, they still have a significantly higher amount of gastric contents.
[SPEAKER_01]: And we think maybe holding one dose isn't really going to matter, and there may be downsides to holding a dose or more, then what are other options?
[SPEAKER_01]: Fast longer.
[SPEAKER_00]: Yeah, so there's another consensus paper, this is not from the ASA, this is a paper by operian colleagues, and they represent the Society for Periodic Assessment and Quality Improvement.
[SPEAKER_00]: They put out
[SPEAKER_00]: a fairytale paper and I recommend anyone who's really interested in this go and read their paper because it goes through the mechanisms that the G.O.B.I.W.
[SPEAKER_00]: and the data from many different studies about residual gastric contents, aspiration risk, and then they offer their recommendations.
[SPEAKER_00]: So in their paper, they
[SPEAKER_00]: only found one study that showed patients clearly did not have any residual gastric contents, and this was when patients were fasted for soft, fasted from solid food for 24 hours.
[SPEAKER_00]: There were 57 subjects in the study, and 100% of them had no residual gastric contents after fasting from solid to 24 hours.
[SPEAKER_00]: So this is the only evidence that we have showing that we can eliminate gastric contents and it's a 24 hour fast.
[SPEAKER_00]: in their study, many other papers with patients fasting 8, 12, 14, 16 hours have all had some amount of residual gastric contents.
[SPEAKER_01]: So it sounds like it is, at least from these studies, it is possible to get the stomach to empty, but it takes 24 hours, not 12, 14, 16.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: So we will be doing for everyone on these drugs, more or less what we're doing for patients
[SPEAKER_00]: you can't have solid food for a while.
[SPEAKER_00]: Now you can still be having your carbohydrate beverages, but that's going to not be a pleasant thing for people under going surgery.
[SPEAKER_00]: Everyone's fasting for 24 hours from solid.
[SPEAKER_01]: And so then the other important point here is solid sources like wood.
[SPEAKER_01]: So what is the, if we say maybe you have to fast for 24 hours from solids, what about liquids and doesn't matter as there are different?
[SPEAKER_00]: That's where we don't have clear evidence.
[SPEAKER_00]: They, because all the studies that I've looked at this have not separated by just solids and liquids, we don't have a clear answer.
[SPEAKER_00]: In their paper, they recommended a four to eight-hour liquid-fast duration.
[SPEAKER_00]: So they specified that if the carbohydrate content was less than 10% they'd like people fasting from liquids for four hours and if it was 10% or more, then eight hours.
[SPEAKER_00]: And this is just based on expert opinion.
[SPEAKER_01]: Okay, so we don't really know how much liquid is safe or now what about liquid content in the stomach?
[SPEAKER_01]: Like do we know how much gastric content of liquid increases aspiration risk?
[SPEAKER_00]: Yeah, so this is where the data gets really interesting and I think that this idea of a tiny question our prior beliefs can be really important.
[SPEAKER_00]: I think it no one would question the idea that solids are increasing the risk of aspiration and if you aspirate on solids, that's definitely going to be more harmful than aspirating just on queer liquids.
[SPEAKER_00]: But this idea that liquid residual gastric contents, how much increase the aspiration risk, is the crox question to me in these patients and to give some evidence about this,
[SPEAKER_00]: on GLP one or a separate next.
[SPEAKER_00]: Over in Europe, many of the pediatric guidelines are recommending pediatric patients only fast for one hour.
[SPEAKER_00]: Now, pediatric surgery is certainly different than adults, so I want to hesitate to extrapolate all of this data to adults.
[SPEAKER_00]: But I use this as an example to say, making we should be questioning how much liquid residual gastric contents are meaningful.
[SPEAKER_00]: This study analyzed three different groups of pediatric patients.
[SPEAKER_00]: It was a prospective multi-center with a total about 300,000 patients.
[SPEAKER_00]: And the groups were divided as patients were in the sift till send group, where they were encouraged to have liquids right up until they were going back for surgery.
[SPEAKER_00]: Then there was the one hour fasting from liquids and the two hour fasting from liquids groups.
[SPEAKER_00]: This is sign as a non-in theory, already study and they found no difference in aspiration group.
[SPEAKER_00]: in aspiration events between the three groups of patients.
[SPEAKER_00]: So this would suggest that consuming liquids before surgery, say this is just water that we're consuming, is probably not harmful and having some not a liquid residual gastric contents in stomach may not be as bad as we have thought it is.
[SPEAKER_00]: But again, this is a pediatric study, and I'm not suggesting that we can use this exact same data, take track of weight to dull sensitive,
[SPEAKER_00]: But I like to use this as a stepping point to say, well, what amount of liquid residual bastard content is harmful in adults?
[SPEAKER_00]: And I'm not sure we know the answer to that question.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: OK.
[SPEAKER_01]: So in the absence of knowing that for sure, what do you think the safest approach is for these patients?
[SPEAKER_00]: I think that the best available evidence we have would suggest the safest approach
[SPEAKER_00]: If you are at a center where you can do gastric ultrasound on these patients, I would highly recommend doing it on all of these patients unless they've fasted from solids for 24 hours.
[SPEAKER_00]: And then you can use your decision tree from there.
[SPEAKER_00]: However, if you're going to do the gastric ultrasound on these patients and the immune you see that they have a full stomach, then you can do it with a full stomach.
[SPEAKER_00]: It still is going to be a risk that you take on as an anesthesiologist if you're proceeding within a elected surgery, especially if it's a mac case and you weren't playing on intaking them.
[SPEAKER_01]: Yeah, that's circuit.
[SPEAKER_01]: And so, you know, it's almost
[SPEAKER_01]: There's got to be some percentage of people who will have a couple of things.
[SPEAKER_01]: Some people may have a false positive, right, where it's the ultimate misread.
[SPEAKER_01]: And so they then have their, they're totally up high risk or maybe even have their surgery cancelled or delayed unnecessarily.
[SPEAKER_01]: And then there's some people who have contents in their stomach who aren't going to aspirate.
[SPEAKER_01]: And so then what, you know, that they may get their case delayed, even though it wasn't going to have any downside for them.
[SPEAKER_01]: And then you have, of course, people who are at higher, or might aspirate, or will aspirate if they go forward.
[SPEAKER_01]: And so it's a little tricky, right?
[SPEAKER_01]: How do you do, do you all just on everyone?
[SPEAKER_01]: And if you do all just on everyone, how do you act on that?
[SPEAKER_01]: So, what do you think?
[SPEAKER_00]: I mean, where do we go?
[SPEAKER_00]: just to take a step back and look at these patients on GOP 1s, the study is looking at whether these patients have a higher aspiration, incidents, are not clear.
[SPEAKER_00]: Most of the studies have not shown a higher incidence of aspiration.
[SPEAKER_00]: Some have, most have, and we always have the issue studying rare events.
[SPEAKER_00]: So maybe they truly don't have a higher risk of aspiration, but that's really hard to show because rare events are hard to study.
[SPEAKER_00]: I think we have to ask ourselves, well, what is the risk that we're willing to take on?
[SPEAKER_00]: Do we want aspiration events to be zero?
[SPEAKER_00]: Or is there some really small percent that is acceptable to balance the inconvenience to patients of fasting for longer durations, et cetera?
[SPEAKER_00]: I think we need to ask, well,
[SPEAKER_00]: clinically, what is this significance of a certain amount of liquid residual gastric contents?
[SPEAKER_00]: And does that increase aspiration, right?
[SPEAKER_00]: This pediatric study would suggest that it probably doesn't.
[SPEAKER_00]: So these aren't easy questions to answer.
[SPEAKER_00]: I would just want people to take home, don't be reassured if a patient holds a dose of these medications.
[SPEAKER_00]: That's not reassuring to me because they still have residual gastric contents.
[SPEAKER_00]: I would say if you're going to use an airway, it's probably better to use an ET tube than a superglot of airway, and it'd be very cautious doing mac case on these patients.
[SPEAKER_00]: That being said, I'm not sure what the best thing is, all these patients coming in and say they're getting their knee replacements under a spinal and back.
[SPEAKER_00]: You know, we have a lot of data now, and you think that if there was a really big signal these patients ask for it and we'd see it, but again, it's hard to show rare events.
[SPEAKER_00]: And the other thing that I think is really insightful to me is that we see a higher amount of residual gastric contents and a lot of these patients who are not in the medications but who have diabetes and obesity.
[SPEAKER_00]: And so maybe we need to take us back and re-value it how we're approaching those patients as well.
[SPEAKER_01]: Yeah, I think this is really interesting and, you know, one thing to think about as you said is what it makes sense to have longer fasting requirements for these patients.
[SPEAKER_01]: Yes, nobody wants to fast for 24 hours, but people do it for colonoscopies, so you know, it's not like on herd of.
[SPEAKER_01]: And if you could have clear liquid, that makes it significantly less onerous.
[SPEAKER_01]: And even a 24 hour water only fast is not the end of the world.
[SPEAKER_01]: So if that makes it safer.
[SPEAKER_01]: So it sounds like there is another area where ideally we have some more.
[SPEAKER_01]: studies that look at things like longer fast and gastric contents that look at risk of aspiration with either different lengths of fasting or with people who hold or don't hold these medications.
[SPEAKER_01]: Because as you point it out, it's not a risk-free thing, holding one or multiple doses of these medicines have risks for patients as well.
[SPEAKER_00]: Yeah, and I think we ought to know approach medicine in this sort of binary way where we don't think about the risks of not making a decision, or we only think about the risk of holding these medications.
[SPEAKER_00]: I'm sorry, I've continued these medications, but we don't think about the risks and holding these medications.
[SPEAKER_00]: And everything has risks on both sides.
[SPEAKER_00]: Our job as anesthesiologist in so many ways is to manage as many risks as we can, but getting to zero risk is not realistic.
[SPEAKER_00]: So where we draw that line,
[SPEAKER_00]: is definitely a place that even in the best evidence people are going to debate.
[SPEAKER_00]: Yep.
[SPEAKER_01]: All right, well, lots of great stuff to think about and you've broken this down really well.
[SPEAKER_01]: Let's turn to the part of our show where we make random recommendations.
[SPEAKER_01]: Do you have something you would recommend?
[SPEAKER_01]: The audience check out for fun.
[SPEAKER_00]: All right, I have a few recommendations, Jeff.
[SPEAKER_00]: I'm a big cook.
[SPEAKER_00]: I love making dinner.
[SPEAKER_00]: And there's nothing more important to me in the kitchen than having really sharp knives.
[SPEAKER_00]: I've gone to my friend's houses
[SPEAKER_00]: I am now that person will sharpen my friends' knives so that they have good knives.
[SPEAKER_00]: So I use this chef's choice, electric knife sharpener, it is gold for being the kitchen.
[SPEAKER_00]: About one's a quarter I take all my knives, sharpen them, it's really quick if you're consistent with this and it makes a world of difference, especially when you're slicing things like tomatoes and all the soft produce.
[SPEAKER_01]: So I could not agree with you more.
[SPEAKER_01]: Is it is this the one that has the three slots, the three slots?
[SPEAKER_00]: Yeah.
[SPEAKER_00]: Yeah, I have it too.
[SPEAKER_00]: Two different ones typically because Western knives and Asian eyes tend to have a different angle of cut, so you can get whichever one fits your knives.
[SPEAKER_00]: It is so good.
[SPEAKER_00]: Totally agree.
[SPEAKER_00]: It makes such a difference to have nice sharp knives couldn't agree more.
[SPEAKER_00]: And then I'll give a book recommendation as well.
[SPEAKER_00]: One of my favorite books is called mistakes were made, but not by me.
[SPEAKER_00]: It's by Carol Taveros and Elliott parents, and this is a great book that touches on some of the ideas that we've talked in this conversation about questioning your beliefs, cognitive biases, and fallacies, and cognitive distance, and why people end up going down these
[SPEAKER_00]: You know, rabbit holes of persisting in their beliefs to spite evidence or making choices that are continuing to cause for their harm even though they don't think of themselves as that's what a person.
[SPEAKER_01]: Awesome.
[SPEAKER_01]: Sounds great.
[SPEAKER_01]: Thank you for those recommendations and we'll include those in the show notes along with the studies that Tyler mentioned earlier.
[SPEAKER_01]: My recommendation is a fun one.
[SPEAKER_01]: So, Dr. Maria Gosling is a CA3 resident at the University of Miami.
[SPEAKER_01]: She's soon going to be a pediatric anesthesia fellow and she wrote a children's book
[SPEAKER_01]: to empower kids undergoing anesthesia.
[SPEAKER_01]: It's fabulous.
[SPEAKER_01]: It is called Toby's magic bubbles and anesthesia story.
[SPEAKER_01]: And I read it, it's really fun.
[SPEAKER_01]: It's about a fish who's having surgery.
[SPEAKER_01]: And I can absolutely see how this would be really nice for a kid who's gonna have surgery in anesthesia to read and kind of get a feel for the fact that this isn't scary and it's kind of can even be fun.
[SPEAKER_01]: So with the support of the community, she's donating books to children's hospitals all over the country.
[SPEAKER_01]: I would definitely check it out, again, it's called Tobie's Magic Bubbles, and Anastasia's story, and we'll put a link in the show notes to that book.
[SPEAKER_01]: And Kudos to Maria for writing a book while being an Anastasia resident, very impressive.
[SPEAKER_01]: Very awesome, that's right.
[SPEAKER_01]: All feed.
[SPEAKER_01]: Totally.
[SPEAKER_01]: All right, Tyler, thank you so much for coming on the show.
[SPEAKER_00]: Thanks so much, Ted.
[SPEAKER_01]: All right, hopefully you got as much out of that as I did.
[SPEAKER_01]: That was really fantastic.
[SPEAKER_01]: Let us know what you thought.
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[SPEAKER_01]: For the ACRAG podcast, I'm Jed Wolpa.
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