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
Revolutionizing Feline Fluid Therapy
Join us as we explore fluid therapy in anesthetized cats with our guests, Drs. Stefania Gelendi and Ben Liao. Discover how mild hypothermia reshapes the way fluids are processed in feline bodies, challenging traditional treatment methods and offering a fresh perspective on veterinary medicine. With insights into feline shock management and the complex interplay of temperature and anesthesia, this episode promises to elevate your understanding of fluid dynamics and the unique physiological traits of our feline friends.
Explore the groundbreaking revelations of volume kinetic analysis as Stefania and Ben unravel the unexpected enlargement of the central compartment during hypothermia. This fascinating development reveals less effective fluid administration. This episode is a must-listen for anyone intrigued by the delicate art of feline fluid therapy.
AJVR article: https://doi.org/10.2460/ajvr.24.09.0279
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You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode, we chat about how mild hypothermia is associated with altered volume, kinetic parameters of an intravenous crystalloid fluid, bolus and healthy isoflurane anesthetized cats with our guests Stefania Gelendi and Ben Liao.
Lisa Fortier:Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today, we have Stefania and Ben joining us. Thank you so much, each of you, for taking time out of your busy schedules to share your podcast with us today.
Stefania Gelendi:Thank you for having us.
Ben Liao:Yeah, thank you for having us.
Sarah Wright:All right, let's dive right in Stefania. Your AJVR article discusses how mild hypothermia is associated with altered volume. Kinetic parameters of an intravenous crystalloid fluid bolus and healthy isoflurane anesthetized cats. Please share with our listeners the background on this article.
Stefania Gelendi:Thank you for the question. So, the study stems from the clinical challenge we face when we treat cats in shock. Cats are especially tricky to treat because of their unique physiology, as you know. So, they're not only prone to bradycardia, hypotension and hypothermia, but also are totally predisposed to volume overload, and this makes fluid therapy a delicate balancing act.
Stefania Gelendi:To better understand how fluid behaves in cats under this condition, we used for our study volume kinetics or volume kinetic analysis. And volume kinetics is essentially pharmacokinetics, but for fluid, and so with that we can analyze how fluid distribute and are eliminated in the body. While there are quite already a few publications on volume kinetics in human medicine, veterinary medicine has only recently begun to explore its potential. The first study was done at Ontario Veterinary College by Dr Zhu and Bettman they're both in my paper and following this, a couple of studies here at Auburn demonstrated its feasibility in healthy cats. So, building on that foundation, we wanted to investigate how mild apothermia specifically impacts the behavior of a fluid bolus in anesthetized cats. So it's worth noting that volume kinetics in itself is not easy, but then the hardest part is actually to identify a relevant research question. So this is particularly true because there is a general lack of evidence in cats, and our understanding of shocks and its treatment in feline patients is mostly based on anecdotal observations, and so this gap in knowledge made us particularly excited about this study.
Stefania Gelendi:But then why hypothermia? We believe that cats, when they experience shock, the body may handle fluid differently. For example, in humans, hypotension slows fluid elimination. That has been demonstrated. But on the other hand, there are some studies saying that hypothermia is still to actually increase urinary production, which is a phenomenon known as cold diuresis, which could lead to faster fluid elimination. However, we don't know if these processes occur at all in cats and, if they do, how they may interact. Additionally, we've been taught that cats in shock often do not respond to fully boneless resuscitations, but there is no really clear explanation for this. So, based on the literature, we know that in anesthetized cats, hypothermia induces bradycardia and hypotension, which clinically mimics the presentation of cats in shock. So, for this reason, our aim was to investigate volume kinetics under conditions of mild hypothermia, and our hypothesis was that hypothermia was low in the distribution, but that cold diuresis would increase elimination, make it faster.
Sarah Wright:Yeah, really important study, so thank you for undertaking this. So what are some important take-home messages from this AJVR article?
Stefania Gelendi:I'll say the big takeaway from our study is that mild hypothermia actually changes how high V fluids are handled in cats and specifically we found that hypothermia increases the central compartment volume, which essentially means that the fluid bolus has less effect on plasma volume expansions compared to when given to a normal thermic cat, and this could make fluids less effective in those conditions. We also found that temperature, body weight and anesthesia all interact to influence fluid therapy in our anesthetized cats and this finding could help us refine how we approach fluid administration in both emergency but also surgical settings. But we need more research to confirm these results and explore how they apply to awake and critically ill cats. Also, contrary to our initial thought, mild hypothermia didn't cause a significant increase in urine output in our study population, so we didn't see any cold diuresis in our cold anesthetized cats. We think that this was due to the effect of anesthesia that might have counteracted that effect, but that's an interesting area for future research.
Lisa Fortier:Yeah, you're so right, Stefania. The cats are so under-researched, so we really appreciate you sharing this with us and our listeners.
Stefania Gelendi:Thank you.
Lisa Fortier:Ben. What's Sorry, go ahead.
Stefania Gelendi:Thank you,
Lisa Fortier:Hey, Ben. What sparked your research interest in fluid therapy?
Ben Liao:Yeah. So, I think I started to have interest in fluid therapy, mostly from. I'm actually more interested in hemodynamic management in a QK setting. and fluid therapy is kind of a topic that kind of connects the dots in hemodynamic management it is a treatment and response different indications and kind of recent interest in the revised Starling principle and glycocalyx kind of reaffirmed my interest in this area. So that's kind of a longtime interest but kind of a recent spark.
Lisa Fortier:Starling's law. I haven't heard that one for a long time. I'm an equine orthopedist. We don't think about Starling's law very often.
Ben Liao:Right.
Lisa Fortier:Stefania, how about you? What sparked your research interest in fluid therapy?
Stefania Gelendi:So actually I started being interested in fluids during the first absolute bad job I got as a new graduate in Italy. At university we didn't really cover much about fluid therapy. So when I attended my first emergency and critical care course, it was in Rome, and I remember the first lecture was about fluid therapy and I was very captivated of it. And then one of the big takeaways was, of course, the fluids are not just basic treatments but they are drugs, so they can save lives when used correctly, but also can cause harm if mismanaged, and so this concept really sparkled my curiosity to learn more.
Stefania Gelendi:And then, when I started my residency at Auburn, Ben introduced me to the concept of volume kinetics, and I remember on the whiteboard he explained it in such a clear and straightforward way that immediately clicked for me. It made so much sense and I thought it was a brilliant idea. So just use pharmacokinetics principle to see how fluid behaves in the body. At first it seemed so simple and straightforward, but then I started reading more about volume kinetics and I quickly realized how actually complicated it is, and I spent about six or even more months just reading papers and studying about volume kinetics just before even starting this project. So yeah, I've been passionate about it ever since, because there's so much to learn and to understand to start with.
Lisa Fortier:Well done, Ben, to fan that flame that was already burning in Stefania Earlier. Stefania then talked about some of the really important findings from this article, but always when we do things, there's things that surprise us. When you were looking at the results and thinking about it, what things did you find surprising when putting this article together?
Ben Liao:Yeah, I think what surprised us was our hypothesis was all on the kind of opposite direction. So in our study basically we found that two compartment models fit our data the best. So essentially and kind of briefly explaining, this is the fluid we gave behaves like there are two compartments in the body, one central, one peripheral, and their micro constant kind of control the rate of fluid going either direction or going out of the body. So that would be the elimination constant. So what we found we thought the micro constant would be changed by the hypothermia but it turns out it was the central compartment that got bigger. So kind of briefly mentioned by Stefania, that that's kind of our key finding and what this means. What interesting is the micro constant didn't change but the central compartment got bigger with hypothermia. So what that means is the fluid is less effective. So when we give the same amount of fluid when the cats are cold, the percentage increase in plasma volume is smaller. So on the other way you can also say this you know that if you give the same amount of fluid, say 10 ml per kilo of bolus, you will induce less percentage increase in the plasma volume expansion in a cold cat, a little bit like when you are pouring a glass of water in an empty pool versus another empty glass. So the percentage increase is much higher when they are normal thermic. So that's very interesting. That's kind of surprising to us.
Ben Liao:But we did have some plausible hypothesis of why this happened. We thought this could be a kind of vasodilation and spleen omegaly from sympathetic activity being decreased and responsiveness decreased. But we couldn't verify this finding based on our study, so that would be something for the future to find out. Maybe we'll combine an ultrasound or CT study to look at the spleen volume or something like that. And another interesting hypothesis we had was if the central compartment would reduce in size when the cats are re-warmed. Like that's our clinical goal, we're clinically trying to not give too much fluid and warm it up and see what happens if you go in and need it.
Ben Liao:So if the central compartment does decrease in size when they are re-warmed, it perhaps can explain why they would show fluid overload once they are resuscitated, because it's like the central compartment being tightened down and the fluid we gave being pressurized and then it started to cause problems like pleural effusion, pulmonary edema, congestion, those kind of things. So we got some interesting hypotheses generated from this study. But this is not a. It's a pharmacokinetic study. It's more hypotheses generating this. What we can do with this study is I cannot really verify all these hypotheses, but it's interesting. All the models are wrong, but it teaches something.
Sarah Wright:That's fascinating. So what are the next steps for research in this topic?
Ben Liao:Yeah, so kind of piggyback on what I mentioned. There are so many interesting research topics. Some of the next steps could be we study the effects of rewarming. So, we just get cat cold, give fluids and then we warm and give another one Kind of compare the fluid volume kinetic between the two states. We can look at the hypothermia effect through the volume kinetic but also at the same time look at the hemodynamic data to kind of have a PKB-TDDR combination. Otherwise, I think eventually all this done in research animals, it would be really more useful to look at clinical patients and that would be kind of a couple interesting next steps.
Sarah Wright:So AI is a very hot topic right now. Do you see a role for AI in this area of research?
Ben Liao:Yeah, I think there are definitely, you know, exploration of using AI in the pharmacokinetic field. There are a lot of interesting direction it is going. I think ultimately, pharmacokware Kinetic is modeling and maybe AI will be able to handle a complicated or complex process. But I think one thing that's kind of critical in my simple mind I'm not an AI expert is that AI is very data-hungry and veterinary medicine is data-lacking. So, it's really hard I think to generate enough data unless there's enough drive to develop really good electronic health system for us to just automatically plug in all this electronic health system that maybe in the long term we'll be able to get all this data, put it into the AI to help us process it. But I think right now I'm just cautiously optimistic.
Sarah Wright:Yeah, yeah, very sure what you said about there being not enough data in veterinary medicine, something that we're definitely working towards and, for those of you just joining us, we're discussing how mild hypothermia is associated with altered volume Kinetic parameters of an intravenous crystalloid fluid bolus in healthy isoflurane anesthetized cats, with our guests Stefania and Ben.
Lisa Fortier:Stefania, you talked about working in private practice in Italy and then a residency in Auburn. How did that training and experience prepare you to write this article?
Stefania Gelendi:Well, this was actually my first time being fully responsible for a prospective study like this one, so it was all pretty new to me. When I started, I had to navigate a lot of different aspects, as you can imagine, from preparing the grant proposal to coordinating with multiple people, organize everything, prepare the study timeline, order, supplies and learn everything about just literature. I also had to learn a lot about how to manage a project on this scale and honestly, it was a real learning experience. There were definitely a lot of times where I would miss details or feel unsure about the next steps, but luckily Ben, as my supervisor, was a huge support. He let me take charge and handle everything on my own, but then he would kind of make sure I didn't go off track. And the other investigators also support me a lot.
Stefania Gelendi:Dr Ewan Battelman and Dr Ravis were always available to clarify volume kinetics concept and also questions I had, as they were the one performing the data analysis and the most familiar with volume kinetics. Dr Johnson oversees the university cat colony that we rented the cats from and helped me organize that. And then Dr Koh and Dr Gerken are actually also my residency mentors and for sure they were there during the most challenging times, ready to provide me mainly moral support but also guidance for the project. And again, it was a real learning experience for me. It taught me a lot about managing a study from start to finish, and I mean it was stressful at times but also incredibly rewarding, and it helped me grow both professionally and personally.
Lisa Fortier:That's a fantastic answer and it's really nice to know from Ben and your other colleagues that mentorship is alive and well.
Stefania Gelendi:Yeah.
Ben Liao:Yeah.
Lisa Fortier:It also gives you a whole other level of respect, when you're reading other research articles, to know how long it took for that team to get that. Maybe one nugget of information.
Stefania Gelendi:Absolutely
Lisa Fortier:Speaking of nuggets of information, if you were going to distill this down, what would be the one piece of information the veterinarian should know about this topic area?
Stefania Gelendi:I feel like veterinarians should know that our experiment model is very different from what happened in clinical shock cases and findings should be verified in a clinical population.
Stefania Gelendi:So, while our study provides valuable insights and it's crucial to recognize that healthy anesthetized cats may not represent what actually happens in cats in shocks.
Stefania Gelendi:However, studying volume kinetics in sick cats is also very challenging, so, mainly in terms of designing ethical and practical studies.
Stefania Gelendi:So, for instances, these studies usually require frequent blood sampling as we need repeated measurements of PAC Cell volume to feed data for the data analysis as input, basically for the volume kinetic model. And this necessitates like this make designing studies that are ethical very hard, because in sick animals you don't want to get all the blood out for all the sampling and so many times. If you want to perform one of those studies in sick animals, you need to go for a terminal study to collect accurate data and personally I find it uncomfortable to conduct terminal studies due to, of course, the significant ethical concerns and challenges they present. But despite these barriers, there's population pharmacokinetics that allow us to model fluid dynamics using like sparse data from many patients, and this approach can help us gather insight without extensive sampling. But yeah, we just need to acknowledge this limitation and highlight the potential for future studies, so that veterinarians can better contextualize our findings and appreciate the ongoing nature of research in this area.
Sarah Wright:So, on the other side of the relationship, what's one thing clients should know about this topic area?
Stefania Gelendi:So I feel like.
Stefania Gelendi:For clients, it's crucial to understand that cats in shock are a significant challenge for veterinarians and their body temperature can affect how intravenous fluids are handled during treatment. And this means that veterinarian needs to carefully adjust fluid therapy to ensure proper hydration without risking all the complications that derive from it. Additionally, our study found that cats' body weight significantly influences fluid elimination, meaning bigger cats showed a decreased elimination rate of fluid, which was quite surprising for us. We don't know if this is a repeatable result, but if it is true, this highlights how important it is of maintaining a healthy weight for your cat, as obesity can complicate fluid therapy during medical procedures, and keeping your cat at an ideal body weight not only benefits their overall health, but also prevents complications when intravenous fluids are necessary. And these findings underscore why veterinarians take extra precautions to monitor and maintain your cat's body temperature and why they may ask or comment about the cat's weight during treatment planning. And by understanding these factors, clients also can better appreciate the complexity of veterinary care and the importance of preventative health measures for their pets.
Lisa Fortier:Really, really well said. Thank you as we wind down again. Thank you both for submitting this to AJVR and for joining us here today on the podcast. We'd like to ask a little bit more of a fun question, so we'll start while we have you. Stefania, if you could have a superpower, what would it be and why?
Stefania Gelendi:I feel like it might sound like an expected answer, but ever since I was a child, I've always wished I could actually instantly communicate with animals. Now, as a vet, that desire is even stronger. Especially when they're in distress and working in emergency and critical care, I often find myself wishing I could truly understand what they're experiencing or what they need in those critical moments. Being able to do that will make a world of a difference, I feel, in providing them with the best care possible. But that being said, after working in the field for a while, I feel sometimes I can actually have full conversations with them, and I think we will end up talking to our hospitalized patients anyway, don't we?
Lisa Fortier:Yes, we do.
Lisa Fortier:Not just our patients, our pets as well.
Stefania Gelendi:Yeah.
Lisa Fortier:Ben for you. What is your favorite animal fact?
Ben Liao:I was thinking about this for a while but I would go with. Octopus has three hearts. That was pretty cool. They have two that pumps blood into the gills and one that kind of just works our regular heart that pumps blood into the whole body. So pretty interesting anatomy and physiology for me.
Sarah Wright:We actually just learned another fun octopus animal fact. Last week on the podcast too, we had an ophthalmologist and she was sharing how they actually might have like a hole in their cornea that provides communication to the anterior chamber of the eye, so really fascinating. But thank you so much, Stefania and Ben, for being here today and for also contributing your manuscript to AJVR.
Ben Liao:Thank you very much.
Sarah Wright:And to our listeners. You can read Stefania and Ben's article on AJVR. 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.
