Is emergence from sevoflurane substantially faster than from isoflurane?

Welcome back to Depth of Anesthesia. This is a podcast that critically explores our clinical practices. I'm David Hao and I'm an anesthesia resident at the Massachusetts General Hospital. This week's episode will be featured on Anesthesiology News, one of the most widely read resources in our specialty. My guest today is Dr. Keith Baker.

Dr. Baker is the current Vice Chair of Education here at MGH, and as some of you may remember, he joined us for episode six to explore the claim that the sniffing position was the best for viewing the gladic opening. If you haven't had a chance yet, give that episode a listen. It's gonna change the way you think about laryngoscopy. Dr. Baker, welcome back to the show. Thanks, David.

Glad to be here. And Dr. Baker, I've always been interested in the work that you've done exploring learning and how to achieve mastery through the expert pathway. Can you just tell our listeners a little bit more about the work that you do? Well, it's all predicated on the idea that much is known about becoming better at whatever one chooses to do, but almost all of the material that is related to that process of getting better at what you do, or performance as I call it, is from fields that are not related to anesthesiology. In other words, very little has been done in terms of research in our field.

But around our field and outside our field, quite a lot has been done, whether it's in sports, music, or other uh chess mastery for example and quite a lot has been done to learn what it takes to become particularly good at whatever one endeavors to do. And so it's it's looking at all of the science of understanding what leads to expertise in particular. And there's quite a lot actually in that regard Yeah, I think it's super interesting because I've had the opportunity to hear you speak about this subject throughout my residency, and I think it relates well to the core mission of the podcast, which is to encourage critical thinking and achieving a higher level of performance in the specialty.

So I figured it'd be nice for our listeners to hear about your research interests in that area. Yeah, it's a lifelong goal and so the one begins the process and continues to learn and learn and add uh to the level of understanding about strategies that one would choose to adopt and apply for performance to prove throughout their career. It's a it's a lifelong process How did you get interested in exploring the subject that we're going to cover today? It probably stemmed from my usual question. How do I know what I think is so to be actually true?

And so at our institution, people typically turn on what I call the yellow drug or siboflorane. And then when uh I ask why they choose that drug versus say isotherane, uh the answer I get is typically something along the lines of, well it gives a faster wake-up and it's a quicker drug. like that. And then the question naturally arises, well how much faster and how much better is this drug than the other drug and how do we know that? And so it takes a little bit of homework in the primary or peer reviewed literature to learn what's out there and a little physics and so on and and uh I was surprised that it wasn't quite so straightforward, the uh the line that I was being told.

It's funny because in the course of doing these podcasts, I've realized that sometimes the toughest claims are the ones you don't even realize are claims, and that's definitely the case for this subject. I think this subject is particularly easy to swallow, so to speak, or easy to take, because there's an element of truth uh in why the claim might be true. And I think that element of truth is then played r repeatedly and has really been adopt therefore been adopted quite widely And so our case today is that of a 25-year-old healthy man who is presenting for an uncomplicated laparoscopic abendectomy. On induction of general anesthesia, the resident turns the dial on the isoflurane vaporizer and the attending notices The attending mentions that it's likely to be a short case and that sievoflorin is probably the better option for a faster wake up.

This is a true story. This happened to me, I think, when I was on overnight call when I was a CA1. I distinctly remember the attending saying, We don't want to be waiting all night for the patient to wake up. Dr. Baker, what are some of the inherent claims in this case? Well firstly, that uh when it comes to short cases, and I I think that's what is part of the structure of this argument.

We have a short case here, typically a laparoscopic appendectomy is about a one hour long type of a case And the concept here is that the drug isoflurane, which is an older drug, is going to cause this slow wake-up. And there are some reasons to believe that that might be true. And so I think that's probably what gives rise to the claim that Sebifluorine, which is the less soluble drug in terms of the blood gas coefficient, uh is therefore going to the assumption is that that will inherently cause a faster wake up. So to our listeners, what's the level of your agreement with the principal claim that wake ups are substantially faster with sevoflurane compared to isoflurane?

And what is the level of evidence for what you believe? Dr. Baker, the first study I believe you have for us to shed some light on this claim is a comparison of isoflurane and sevoflurane anesthesia in the outpatient gynecologic surgery setting. Well, importantly, uh, this particular study had uh essentially healthy people coming for what I'll term uh short operative procedures uh in the GYN uh domain And so, you know, this is looking at sort of a one-hour-long procedure type thing. So again, this concept of short comes up. Importantly, these people were randomized, so cause and effect ought to be available in our conclusion.

And These people were matched to their so-called BIS score. So the concept here is that by using a BIS monitor both groups would be sufficiently and equally anesthetized, getting around the whole concept of m accidentally running one group deeper than the other. So at least they tried using modern technology to make the level of anesthetic during the case, the maintenance phase, to be identical. Furthermore They turn the drugs off at the end. There was no taper of the ISO or the SIBA fluorine.

Most anesthesiologists begin to see the end of the case coming. They start to make adjustments by reducing. The level of volatile anesthetics or switching over to nitrous oxide or switching over to propofol. But in this case, they kept people at the full MAC until the case was finished They turn the dials off abruptly and then ask the question, which drug is faster or slower in terms of wake-up? So it looks like after the volatile was discontinued, the patient's name was then called out at 30-second intervals, and some variables they looked at included time to opening of eyes. obeying commands and orientation, as well as some markers of readiness for discharge.

What did they find in terms of differences between the two groups? Uh uh essentially nothing. Meaning no differences that were worth talking about. Yeah, so basically no statistically significant differences in any of the parameters. And it looks like the duration on average was about 60 minutes in the isoflurane group and 52 minutes in the sevoflurane group Yes, so again this concept of shorts.

So people have talked about ISO and CIVO being particularly different in short cases. And here we have an example of a very classic short case. Measurements were made on both groups, and there is no important difference. in the wake-up speeds by all conventional measures and in their duration uh to being ready to go home I I think this study was also included as part of a broader systematic review where they looked at the recovery profile of propofol, iso, sevo, and desflorain after ambulatory anesthesia. Did that systematic review add anything different? Yes.

They brought up in that review that there are some publications that show small, but measurably true speed advantages to Sievo Florent, particularly on the wake ups. These are in the order of maybe two minutes or something for these short cases. So a number of studies have found measurable, short, and in using their own words, basically clinically insignificant advantages to CIVOFlorin. I think that speaks again to the distinction we often talk about between clinically and statistically significant. Right.

So uh the critical component here is that the claim that SIBA fluorine yields a faster wake up, technically speaking, is true. However, it's the interpretation of its importance and its magnitude that uh is where the differences in behavior come in because I think that the differences uh are small, clinically small, for all measures that they've done, whether it's the wake-up time or the recovery room time, they're all very small differences. And there is, at the same time, a financial disadvantage to using that very same drug. So far all these studies have been in the ambulatory setting. I'm curious as to whether a distinction starts becoming more clear with extended anesthetics. questioned and that was a study by uh a group looking at neurosurgical patients and these people were randomized to Sebiflurane or isoflurane.

And importantly, these cases were nearly six hours or even slightly longer uh on average. So these are these are substantial operative procedures. And uh the way they conducted the procedure, the study that is was to maintain the patients on their anesthetic at nearly a full MAC until the case was completely done and the dressing was on. In other words, the surgeon had stepped away from the table, so to speak And at that point, they turned the flows on or turned the flows up, the fresh gas flows, I mean, and then they turned off the vaporizers in a very abrupt manner, no tapering And in that case, indeed, the wake-up for isoflurane was on average 10 minutes slower than sevoflorane.

I do want to emphasize that there was no tapering involved. This is probably not what you would expect to happen as isoflurane is generally tapered earlier in a typical clinical setting. So basically at the end of the case both volatiles were turned off at the exact same time. Yes, exactly. So this is sort of the, I would call it the worst case scenario.

Importantly, uh the duration to readiness to discharge from the recovery room was the same between these anesthetics. So knowing that the evidence seems to suggest the lack of a substantial difference in wake-up times, especially for short cases, what else factors into selecting isoflurane or sevoflurane? Yeah, there are a couple of factors. Firstly, this is a good segue into discussing the very particular aspect of the case that I'm currently speaking about, that is maintenance phase. When it comes to a volatile anesthetic induction or so-called breathed down, then I think you'll find the SIVO fluoride is the distinctly superior drug, both clinically in our experience and in the literature.

So uh if one has an interest in performing a uh a breathdown, as we call it, then sevoflurane is the is the drug to use, and isoflurane is notably more difficult, more coughing, muscle much less uh pleasant for the patient, more uh um misbehavior as I call it uh by the patient. So uh we're not talking about a breathe down here. We're talking about maintenance phase of general anesthesia after an IV induction. That's really where this entire value proposition and ISO versus SIVO comes into play. But in terms of cost, many people use SIVOFlorine at the two-liter fresh gas flow, minimum flow rates, and they will use much lower flow rates for isoflurane.

So there's also the MAC difference. So Sivafluorine is twice the percentage the as isoflurane And then there's the acquisition cost by the institution to get these two different drugs. So in each case, everything is uh cheaper for the isoflurane. So you can buy the stuff cheaper. uh per per gram, so to speak, per bottle. Uh you can use distinctly lower flows with nobody worrying about any elements of fresh gas flows.

And you have to use less of it because it's a more potent anesthetic than is sievafluorine. So all of the uh features of the use of the drug favor isoflurane in a financial sense So I think the classical teaching about sevoflurane and isoflurane is that there's a distinctly lower blood gas partition coefficient with sevoflurane. that should theoretically lend itself to a more rapid recovery from anesthesia. Do you think there's a misconception about the role of that in recovery and that's why we're seeing differences in the actual clinical recovery characteristics? So I I think what people have done is taken that blood gas partition coefficient difference, which is about twofold. In other words Isofluorane is twice as soluble uh compared to sevoflurane, then that's true.

That that's a very reliable finding The problem is that there's much more to it than that simple number. And if it was only the blood that had the sevoflurane and the isoflurane in it, then indeed you would have a very reliable faster wake up from Sebofluorane. However, as soon as the the volatile anesthetics are absorbed into the blood They're then transferred through the cardiac output to the muscle and the fat. And it turns out that the blood fat and the blood muscle partition coefficients for these two drugs are essentially identical. They differ by no more than a couple of percentage points between their the blood blood muscle and blood fat coefficients.

So importantly, during the anesthetic that's being conducted, as we absorb isoflurane or sevoflurane into the into the blood, it's taken out and stored in our fat, in our muscle And then at the end of the case, when we turn the anesthetics off, we degas the blood, and it does degas more rapidly from the siebofluorane patients. However, the muscle and the fat then begin to diffuse the stored gas back into the blood and that's the slow wake up right there. And since those partition coefficients between those tissues that are essentially identical, that is the nature of this of the very similar wake ups between these two drugs. If I'm hearing you correctly, the low blood gas solubility coefficient has a role, but it sounds like there's been too much emphasis on that being the only factor.

Correct. In terms of if you think of a kinetic reaction in chemistry, we always talk about the rate limiting step. And there may be a number of steps that are very rapid in a chemical reaction, but the one that most people care about is the rate limiting one because that's what determines the overall speed of the reaction And in the case of sievafluorine and isoflurane, the blood gas is but one element out of numerous uh compartments that are being gassed or degassed during the process of going to sleep and waking up And so I think the rate limiting step here is largely dominated by the blood muscle and the blood fat coefficients, which I say are basically identical.

And then what comes into play at the later part of the chain of of of sequences is the the blood gas where sievoflorine does have a real measurable speed advantage, but not being that since it's not the rate limiting step in general. We're not seeing the rapid speed that that one would naturally think might occur. Got it. That makes a lot of sense. Do we have any institutional information about sievafluorine and isoflurane cost differences?

We do. We we had one of our uh residents uh explore this some years ago, and because of our uh electronic medical records, they were able to minute by minute calculate both fresh gas flows and the inspired concentration of the volatile anesthetic and then integrate that over the entire duration of the case and then do this for thousands and thousands of cases using both semifluane and isoflurane Knowing our acquisition costs, they could then calculate how much money was spent on average for a case using isoflurane as compared to sevaflorine. And at our institution A few years back, that ratio was about tenfold, meaning it was ten more ten times more expensive to conduct a volatile anesthetic made out of sievafluorine than one made of out of isoflurane.

So There are other institutions where they've repeated this and depending on acquisition costs and flow rates, those ratios may be five to one or so, but distinctly more expensive to use the SIBO fluorine. That's pretty striking, and you can imagine how that scales in a large institution. Dr. Baker, would you be able to summarize some of the evidence we've discussed today? Yeah, sure. Importantly, there is some, again, there's an element of truth in the claim that you will have a faster uh wake-up, so to speak, if you see the fluorine than isoflurane.

A number of studies have shown that, both for a short one hour or two hour case where the difference might be one or two minutes, all the way up to the six hour or seven hour case where the difference may be up to ten minutes. Importantly, the way those wakeups are conducted, they are at a worst case scenario, meaning you're taking your patient to the very end of the case on a full dose of anesthetic and after the case is complete turning the anesthetic off. So they really are what I would call a novice level anesthetic where you don't even plan for the end of your case. So that's worst case scenario. And in all of the cases, the differences I say again are re reliable to the tune of one or two minutes And in general, the the the time that it takes to get ready to go home is oftentimes the same between SIBA fluorane and isoflurane in terms of the uh the general wake-up period in the recovery room.

So there are differences. but they are very small and the cost ratio uh is distinctly different between these two and is something to consider in today's financially uh minded medical uh environment. In fact there was just a study that came out in anesthesia and analgesia earlier in 2020, just earlier this year where they actually did this comparison doing two weeks of isoflurane anesthetics for all their patients having colorectal thyroid and parathyroid surgeries, followed by two weeks of Civafluorine anesthetic for all the same sorts of patients And they put together about 1,500 patients who had either isoflurane or sebofluorane and really found that the differences clinically were quite small and not to be uh uh not to be worth talking about.

And uh since they found that their cost differences were notable, they make the claim that one can do a very reasonable anesthetic for a lot less money using isoflorin Yeah, and as I briefly mentioned before, the financial implications can really be magnified when you scale to the institutional level or higher. Yeah, it does. Uh it's interesting that uh people have used their their understanding of the drugs to make their decisions. So almost almost invariably the claim is made that Sevoflurane is faster and you get a very slow wake up if you use isoflurane. And I don't think the data support that, other than to say there is some small element of truth there But the money is something that we don't put into our calculus and we just go about the fact that it might be one or two minutes faster, or even three minutes faster, for example.

But even then, it's a very small difference. I've heard people too claim that the price of an operating room is so high that it more than offsets any uh slight slight cost savings you might have by using isoflurane versus sevoflurane. For example, you hear people say it costs $60 a minute to run an operating room and three minutes therefore equals a lot of money. But that is not how the economics of operating rooms work. Uh quite a few people have written about the economics of running operating rooms.

And that simple concept of taking how much it costs for a day and dividing it by the number of minutes is a completely inaccurate and in incorrect model of the finances of how operating rooms work. So That is a very misleading way to interpret uh time in an operating room. Sounds like another episode is in the making. So to our listeners, what's the level of your agreement with the claim that wake-ups are notably faster with SIVO compared to ISO? And what is the level of evidence for what you believe?

Dr. Baker, thanks again for taking the time to join us on the show. I really enjoy digging into these claims because I think they're so fundamental. Just like the sniffing position as being best for viewing the glodic opening, I think this claim is entrenched and it's really going to benefit our listeners from just thinking more critically and understanding the evidence behind these claims. Always a pleasure, David. Thank you.

Thanks for joining us on this episode, and thank you all for continuing to email me with your episode suggestions. I hope all of you guys continue to care for yourselves and each other in these difficult times. Stay hungry and keep asking questions.