Veterinary Vertex
Veterinary Vertex is a weekly podcast that takes you behind the scenes of the clinical and research discoveries published in the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR). Tune in to learn about cutting-edge veterinary research and gain in-depth insights you won’t find anywhere else. Come away with knowledge you can put to use in your own practice – along with a healthy dose of inspiration to remind you what you love about veterinary medicine.
Veterinary Vertex
Amikacin Concentrations in Healthy Neonatal Foals
Curious about the scientific evidence behind treating joint infections in foals? This eye-opening conversation with Dr. David Wallace explores groundbreaking research validating common clinical practices while revealing surprising limitations.
Septic joints in foals present a clinical challenge requiring both local and systemic antimicrobial therapy. Until now, veterinarians have largely extrapolated treatment protocols from adult horses without solid evidence supporting these approaches in neonatal patients. Dr. Wallace's research addresses this critical knowledge gap, examining whether concurrent intravenous regional limb perfusion (IRLP) and systemic amikacin administration achieves therapeutic concentrations in both compartments.
The results offer reassurance that splitting the amikacin dose—one-third for regional perfusion and two-thirds systemically—effectively treats both joint infections and underlying systemic disease. Most joints achieved therapeutic concentrations, though significant challenges emerged with hind limb perfusions. The metatarsophalangeal joint consistently failed to reach target levels, revealing important technical limitations around tourniquet placement and vascular integrity that clinicians should consider when treating these patients.
This conversation highlights numerous opportunities for future research, from evaluating alternative tourniquet designs to determining appropriate dose adjustments for multiple affected limbs. Dr. Wallace emphasizes that individual patient response remains paramount, reminding us that "foals are not small horses" and require specialized approaches. Whether you're a practicing veterinarian, student, or equine enthusiast, this episode provides valuable insights into evidence-based care for our youngest equine patients. Subscribe now to stay updated on the latest advances in veterinary medicine!
JAVMA article: https://doi.org/10.2460/javma.24.10.0678
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Speaker 2:This is Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about how concurrent intravenous regional limb perfusion and systemic amikacin achieves variable synovial fluid amikacin concentrations and healthy neonatal foals with our guest, david Wallace.
Speaker 3:Welcome listeners. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright and David hey. David, thanks so much for taking the time to be with us here today. I know you're very busy wrapping up your residency.
Speaker 4:Thank you, guys for having me. It's an honor to be here.
Speaker 2:All right, let's trot on over. So, david, your Javma article discusses how concurrent intravenous regional limb perfusion and systemic amikacin achieves variable synovial fluid amikacin concentrations in healthy neonatal foals. Please share with our listeners the background on this article.
Speaker 4:Yeah. So we know a lot about regional imperfusion use in adults, and I think what a lot of people are doing is kind of extrapolating what we do know from adults and using it in foals. So kind of what we set out to do was to try and look at the most common techniques that are used and try and figure out, like, is it truly reaching the concentrations we want? And so we looked at a couple of older articles that are looking at, you know, appropriate doses for falls at that age, what MICs we're trying to accomplish, both synovially and systemically, to make sure we're treating systemic infections that pretty commonly lead to synovial sepsis, and then just try and make sure that we're hitting those markers as often as possible.
Speaker 2:I come from the zoo world where we're always trying to figure out like does this drug actually work in the species? Is it reaching therapeutic levels? So I have a very healthy appreciation for studies like this. So definitely worthwhile. And what are some of the important take-home messages from this article?
Speaker 4:Yeah. So I think the most important thing that we found is that it does work. I know what a lot of people that I talked to beforehand. They were concerned that by splitting the dose, like we did in this paper, is going to take away from the systemic concentration that you're going to achieve and you would be short-changing the treatment of, let's say, on fallopalbitis or pneumonia or something like that. And so what we found is that by splitting the dose a third in the regional perfusion and two-thirds systemically we are reaching appropriate systemic concentrations for continued use.
Speaker 4:We are getting close to the trough concentrations to allow for 24-hour dosing. We're a little bit above what we'd like to accomplish. So that might need to be looked at to see if, like if you're going to be dosing this multiple days in a row is there going to be buildup of the aminoglycoside. But then, on top of that, we're also reaching appropriate synovial concentrations in most of the joints that we tested. There's a couple caveats, I think, to that statement, but it is shown to be effective at the doses that we've used with the splitting that we did in this treatment.
Speaker 3:David, I really applaud you guys for putting some evidence behind something that we've been doing, as you said, empirically for a long time. What sparked your research interest in this topic? Did you have a foal that had a resistant infection or did you end up with some nephrotoxicity? What really sparked like, oh, we need to look into this and make sure it's legit?
Speaker 4:Yeah. So I think kind of, in talking as a resident, I needed a research project and so trying to come up with what we wanted me to do. Coming into the residency I did a ton of internships and so I've seen a ton of different ways to do regional perfusions and falls. Everyone has their own cocktail, everyone has their own technique that they want.
Speaker 4:Um, and our internal medicine clinician at OSU actually had a question about this because they were wondering if you have a horse that has multiple legs that have synovial sepsis and you're trying a dose splitting like what's appropriate, and we were like, well, before we try and dive into that, we need to make sure that it works, just doing one leg. Umoonover is my mentor and he does done a ton of work in the realm of adult IV, regional and perfusions, and so this kind of seemed like a natural next step to go to foals and I just realized this is a huge hole in the literature and we need to start down the path of trying to figure out what's appropriate for foals when we're trying to use these techniques.
Speaker 3:Yeah, very important. Mike's a great mentor. I'm glad you found him.
Speaker 4:Yeah, I like working with him.
Speaker 3:Always when Sarah asked you a little bit earlier what were some of the most important findings. But every time we do a study like this, we find things that surprise us, that lead to more studies. So when you and Mike were doing this one, what did you find were some of the most surprising findings?
Speaker 4:So I think the most surprising finding that we found was that the hind limb that we were treating for regional perfusions had a couple of problems that kind of muddied the waters of some of our findings. And so specifically the hind limb, fetlock or the metatarsal phalangeal joint, almost all of the falls, you know, there were maybe one or two that actually reached appropriate concentrations, but for the vast majority of them they were well below even the low end of the target that we were trying to achieve. And you know, looking further into that, we have questions about why that might have happened of the amikacin while the perfusion was going, and we did find a pretty significant amount of venous escape or bypass of the tourniquet. And so the question is, you know, is the tourniquet ill-fitting because the gas can shape, is a little bit irregular. So you know, if we were to redo this study or if someone was to do another study, it might be worth looking at, you know, extra padding or looking at the difference between a wide rubber tourniquet or pneumatic tourniquet that we used.
Speaker 4:Also, six out of the eight legs that we perfused had rupture of the saphenous vein at some point during perfusion and so we got really high doses or concentrations in the tarsacurral joint, but very low concentrations in the metatarsophalangeal. And so the question there is is it just because it was so extravasated that it just diffusely or passively diffused into the joint that was near and kind of took away from what could go more distally? Or is it that we need a higher volume in the hind limb because it's got a higher cross-sectional area? So we've got a few kind of, you know, inconsistent things that we could try and tighten up, I think, in the study design to try and prove that this technique does work there. But I think that's probably the first thing that we need to investigate.
Speaker 3:Yeah, tourniquets around the hawk are hard for adults in surgery, right If you're doing a hind limb tenoscopy or anything? So hopefully you and Mike are in the woodshed figuring out some better way to get a hind limb tourniquet on a horse in the hawk region.
Speaker 2:So, david, you kind of alluded to this already about some future areas of research, but what are the next steps for research in this topic?
Speaker 4:Yeah, I think this is probably the most exciting part, because we have essentially just opened the door a little bit and I think a lot of people can take this a ton of different ways. I think the first thing that we need to look at is probably that hind limb and see, like you know, is the tourniquet need to be extra padded? Do we need to look at um like a meta-analysis came out for adults looking at the difference between wide rubber tourniquets and pneumatics that might need to be investigated in the falls to see if one is more appropriate than the other? Um, looking at, uh, different drugs instead of just aminoglycosides, um that can be used for perfusions Probably the most important next step. For you know we've done this in healthy neonatal foals. Now we need to start doing it in actually clinically affected foals, because we know that foals that are clinically affected are going to have different metabolism rates of aminoglycosides. It's also going to change as they age up, so we may need to look at dose changes as they go from neonatal to kind of pre-weaning, to weaning, to yearling ages.
Speaker 4:I think that's something that needs to be looked at. And then one of the big ones is if we have more than one leg that's affected. How are we going to further split that dose? Because we're going to keep taking it away from systemic. At least this way it has treated the systemic infection, or at least it suggests that it will. But if we take more away from the systemic dose, is that going to actually further drop that down, and so I think we need to look at that as well. So I think that's really exciting that you know we've got kind of the baseline study design and now we everyone can just run with it and, you know, try and fill in all these holes have you and mike started any of those studies yet?
Speaker 4:not yet. We have some ideas and we have a new resident coming in starting in july and he's already starting to kind of pull together something and try and get her on to doing that one. So we do have someone trying to do that. Um, I want to go into academia, so I think that this is nice, that I can kind of latch onto this and maybe make this the rest of my career if I have to do research in academia, just keep hammering out these finer points.
Speaker 2:Lots of great ideas. We hope to see many more manuscripts from you then in Javma. And do you see a role for AI in this area of research? And do you see a role for AI in this area of research?
Speaker 4:Yeah, this is the harder one that I was trying to come up with because, you know, growing up I read a lot of Isaac Asimov and AI scares me.
Speaker 4:But I do think that there is a place for it, especially in the data coalition, because one of the hardest things that I had to do, you know, in between performing all the profusions and then writing the manuscript, was the data, you know, just sifting through it, and it's a lot of numbers to try and get through.
Speaker 4:So I had a hard time trying to sift through and find, you know, if there were lab errors that you know one number didn't fall in line like it would make sense to, and then we would send backup samples to retest those. So I do think that, like some sort of AI would help kind of collate that data, find those outliers that might need to be retested to make sure that it actually, you know, is that number or was that a lab error that needs to, you know, be reassessed, and then you know, aid in just kind of getting some of the statistical analysis started and then still have a statistician kind of you know, double check. All those things. I do think it can help a lot with, you know either data coalition specifically, study design, I think in certain areas as well. But I do think that that will kind of start to have a bigger role as it gets a little bit more improved.
Speaker 2:Yeah, it'll be super interesting. I think that's definitely one of the more common answers that we receive, so if any of our listeners have any ideas, definitely let us or authors know. And for those of you just joining us, we're discussing how concurrent intravenous regional limb perfusion and systemic amikacin achieve variable synovial fluid amikacin concentrations with our guest David.
Speaker 3:Hey, david, you talked about doing a few internships and that kind of sparked the idea for this manuscript. But how did your training or other work prepare you to not just design the study but get the study done, cross the finish line, get the manuscript written and submitted?
Speaker 4:Yeah. So I think I was very fortunate in having a lot of internships and very high volume practices so we saw a whole bunch of foals with septic joints when I was in Kentucky. So I've done you know, almost probably hundreds of you know full IV regional imperfusions, which helped me in the study design because we initially had tried to do this under sedation and I remember back that everyone I've done in a clinical example was under general anesthesia. So after getting kicked in the stomach a few times by the half sleep full, it was like, okay, maybe we just anesthetize them because that's clinically what we're going to do anyway. But I got a lot of skills in you know doing the regional perfusions.
Speaker 4:I got to work with a ton of different veterinarians who all have different ways of you know viewing what the appropriate dose splitting is. I talked to a few who sparked the concern that well, if we're taking away from systemic dosing, are we shortchanging them? And or if we're giving a full dose systemically and a partial dose regionally, are we overdosing them and potentially setting them up for nephrotoxicity? And so just getting the opportunity to work with so many like really well-known veterinarians, getting all the different pieces of you know empirically what they think works and just going. Well, I guess maybe I should just go and figure out what actually works and then to work with Mike Schoonover, who has done a ton of work in the realm of regional imperfusions already and he already had, you know, some connections with different labs to do the assays, just kind of help, you know, fill in those gaps and made it very easy to just kind of run with it once we got the project started.
Speaker 3:Have you had the opportunity to share this data in this manuscript with those other doctors that you worked with in your internship and gotten their support or swayed them perhaps?
Speaker 4:Not yet. I was waiting for it to get accepted so I could prove like, hey, it's actually going to get published. And then I was going to send it to him or at least call him and just be like hey, I got this paper published, just want to know what your thoughts are on it. And if you think that we missed something or need to go another direction and prove something else, like, let me know because I want to do more on it. So we've got more holes to fill and I would welcome all Sure, sounds like you're the next leader, though.
Speaker 2:Yeah, I love that you're open to feedback too. That's awesome. Now this next set of questions is going to be very important for our listeners, and the first one is going to be about the veterinarian's perspective. What is one piece of information the veterinarian should know about amikacin concentrations and healthy neonatal foals?
Speaker 4:I think the first thing to know is that at least this technique we know works. That doesn't mean that other techniques probably won't, and probably should look into that. But we did find, you know, check that we could make sure that the tourniquets were in place no joint achieved in the even near the appropriate therapeutic dose that we wanted, and that's, I think, just an individual response. And so I think it's very important that, even though you're using this, these techniques that have been, you know, shown to suggest that they work, response to therapy is going to be very important. And so if you are doing the same thing over and over and not achieving any sort of progression in the case, it might be because that horse is not going to respond appropriately and we need to go to a different technique, whether it's direct intra-articular injections or use a different antimicrobial. So I think that's important to know that. You know this isn't the end-all, be-all treatment.
Speaker 2:But on the other side of the relationship, what's one thing clients should know about this topic?
Speaker 4:I would probably say about the same thing, because, you know, anytime a veterinarian tries a therapy and it doesn't work, you know it's very frustrating for the client. I think it is important for them to realize that there is an individual variability to the response of any therapy that we're going to do and to just, you know, be patient. You know we're going to keep checking all of our vitals, keep checking cytologies and things like that, to ensure that we're making headway, and know that if we aren't, we're going to pivot and try something else. And so I think it's just important for them to just kind of, you know, have a little grace and be patient with us as we try to sift through some of these. You know, nuances with, especially with foals they're, you know everyone thinks that they're small horses and they're not. They're their own thing.
Speaker 3:They definitely are. And if you only got kicked in the stomach when they're under sedation, try to do this, you're doing pretty well and it is pretty silly, you know, when you think it takes somebody on the head, somebody in the forearm, somebody in the hind limbs and the tail and then you to do the regional.
Speaker 4:So it's just like a waste of these falls and getting them anesthetized so that once they were still, the manpower didn't need to be quite as high, so I've really enjoyed working with everybody on this project.
Speaker 3:Yeah Well, david, I really enjoyed speaking with you and Mike at the conference and over your poster, and so glad I convinced you eventually to submit this to JAVMA, and I've learned more from you today too. So thank you for agreeing to be on our Veterinary Vertex podcast.
Speaker 4:Thank you guys for having me. It's been great and it's a great honor. It's the first time I've ever been recorded for something, so it was great.
Speaker 3:Very good. As we wind down, we like to ask a little bit more of a personal question.
Speaker 4:And most of the time this dates people, but we'll and we're always surprised too. Uh, what is the first concert you attended? So I went and saw acdc when they did the black ice tour. Uh, that had to have been 2008, 2009. Um, I grew up listening to classic rock, so I love acdc, and it is only the first concert that I went to, because I tried to go to Led Zeppelin's reunion concert back around the same time and I didn't get pulled for the drawing. So that would have been it and that would have. That is my absolute favorite, so I wish that was my first one.
Speaker 3:You know, ACDC is on tour again this year.
Speaker 4:And I am tempted to. If I weren't still a resident, I would have be tempted to go watch, but I'm afraid I'm probably going to be on call that weekend.
Speaker 3:Yeah, they're selling out all over. I still need to look up and get tickets somewhere.
Speaker 2:It's so hard to get concert tickets nowadays it's crazy. So best of luck to anyone who tries. Well, thank you so much, David. Again, just echoing Lisa, we really appreciate you being here today and for sharing your research with us too.
Speaker 4:Thank you guys for having me.
Speaker 2:And to our listeners. You can read David's article on Javma. I'm Sarah Wright with Lisa Fortier. Be on the lookout for next week's episode and don't forget to leave us a rating and review on Apple Podcasts or whatever platform you listen to.
