Reevaluating Liposomal Bupivacaine: Insights and Implications for Canine Pain Management

Join us as Drs. Vanna Dickerson and Danielle Hollenbeck discuss the impact of peri-incisional liposomal bupivacaine on postoperative pain scores, opioid use after soft tissue surgeries, and incidence of incision site complications in dogs. Despite its widespread use, liposomal bupivacaine may not be providing the pain relief many expect. With 83 dogs enrolled in their study, these findings challenge the status quo in veterinary medicine, emphasizing the importance of evidence-based care and cost-effectiveness. These revelations could reshape clinical practices, especially in cases where traditional analgesics fall short. Explore the nuances of their study and the broader implications for veterinarians striving to enhance patient outcomes.

JAVMA article: https://doi.org/10.2460/javma.24.09.0589

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Chapters

• 0:01 Effectiveness of Liposomal Bupivacaine in Dogs
• 11:35 Veterinary Research and Personal Insights
• 16:46 Researcher Interview on Javma Publication

Transcript

Sarah Wright: 0:01

You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode, we chat about how the use of peri-incisional liposomal bupipacaine was not different than placebo regarding pain score or rescue analgesia and a randomized clinical trial of 83 dogs, with our guests Vanna Dickerson and Danielle Hollenbeck.

Lisa Fortier: 0:22

Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Vanna and Danielle joining us and Danielle's hot out of the surgery suite, so thank you both for taking time out to join us here today.

Vanna Dickerson: 0:37

Thank you for having us

Sarah Wright: 0:38

Let's dive right in. So, our listeners are familiar already with periancisional liposomal bupipacaine, or NOSIDA. We've talked about before on the podcast. So, we're really excited to have you guys here and offer your perspective and share findings from your study. So, Vanna, your JAVMA article discusses how the use of periancisional liposomal bupipacaine was not different than placebo regarding pain score or rescue analgesia in a randomized clinical trial of 83 dogs.

Sarah Wright: 1:07

Please, share with our listeners the background on this article.

Vanna Dickerson: 1:09

Yeah, absolutely so. I exclusively do soft tissue surgery. So you know we end up with the patients that either maybe we're doing GI surgery on or they're not as stable. So I think anytime there might be an option that we won't have to worry about as many side effects, with that's going to provide analgesia, we're super interested in it. So because of that, liposomal bupivacaine was definitely something we were excited about and we're using it a lot. But when we started kind of thinking about the plan for this study, it was around 2020. So really the only studies at the time were in stifle surgery. So that was kind of what made us decide to do this study. Was wanting a little bit more objective data on if we're going to use it in different scenarios like our soft tissue surgeries. Is it actually being as impactful as we think, especially because it's definitely not cheap?

Sarah Wright: 1:59

Yeah, it's a really good point to bring up. I know that's a big point when I've even talked about it before, like with surgical planning and like anesthesia plans as well, like do we use it or not, and cost is a big factor, especially when it comes to, like certain clientele and such yeah. So, what are the important take-home messages from this JAVMA article, Danielle?

Danielle Hollenbeck: 2:18

Yeah, I think the biggest thing for us was that we found that the periancisional liposomal bupivacaine wasn't significantly different from just a placebo of saline for the dogs that needed rescue analgesia and what that means is an opioid injection after surgery and that wasn't different for any time point after.

Danielle Hollenbeck: 2:41

So for us what we were using was the Glasgow composite pain scale and that is something that the technicians were trained on, but different ICU technicians were doing the pain scoring. So we kind of wanted to make it as realistic for how we would be evaluating these pets after surgery and when we would assess do they need a pain medication or not? So you know, we were very commonly doing this, like Dr Dickerson said, with the giving the injections of noceta post-operatively for soft tissue surgery. So we always want to know are we doing something that's helping in any way or hurting in any way? Especially with the cost of nocita at our institution being for like a 25 kilogram dog. It was about $177 for their dose of liposomal bupivacaine and that's compared to 0.5% bupivacaine, which is about 370 for the equivalent dose. So just kind of always looking at the cost benefit for everything that we're doing

Lisa Fortier: 3:46

370, meaning $3.70.

Vanna Dickerson: 3:50

Yes so a lot less.

Lisa Fortier: 3:55

Yeah, it's oftentimes. You know. Everybody wants the best analgesia for their animals, so we just keep adding more and more and more things and doing something that's not effective is not, it's not considered safe. If it's not effective, right, Things can go wrong with injections. But I'm interested. Vanna, you and Danielle and myself are all surgeons and oftentimes the research in analgesia falls over towards the anesthesia analgesia service. What sparked your research interest in this topic?

Vanna Dickerson: 4:30

Yeah, you know, like you said, I think as a surgeon, I hope we're all very interested in our pain. You know pain of our patients and so you know I guess for me it really was, you know the, the classic like the septic abdomen that you've had to do an intestinal resection, anastomosis. You really don't want to give them an NSAID and I feel like there are more options becoming available to us, things like Tylenol-3 that we used to not use as often, or even pregabalin, but really our options are more limited. So that's kind of why I really wanted to look at this and it also was something, you know, in my training. We didn't use it very often, but we were using it way, way more when I came to Texas A&M as faculty. So that was also part of what you know sparked my interest is just kind of seeing, hey, could we be doing better or not?

Lisa Fortier: 5:16

So yeah, very good. Danielle earlier Sarah asked you what maybe were the most important findings, but always when we do studies, we find something we didn't expect. What were some or one or two surprising findings from your article?

Danielle Hollenbeck: 5:31

Yeah, I think the biggest thing was that we were using this a lot. We found that it wasn't significantly different. So we've gotten away from using it and just going back to that kind of evidence-based medicine approach. But I think, looking into this, both on the human side and anesthesia and some other studies, I think the relevance for the general practitioner would be. You know, there are studies out there like the Wheeler paper that looked at liposomal bupivacaine compared to the 0.5% bupivacaine in spays and they were using the just regular bupivacaine as a splash block and that study did note that those dogs did need significantly less rescue analgesia after getting the actual infusion of the liposomal bupivacaine.

Danielle Hollenbeck: 6:26

And at our institution we're very commonly using multimodal analgesia and local blocks, you know, and that standard approach wasn't changed for the study. We wanted to do it how we normally would. So I think that just kind of goes to show that there may still be, you know, in general practice some uses for this. I think the other caveat to that is we're using a multi-dose vial for the liposomal bupivacaine, so being able to handle that sterilely we do that in a hood, things like that. So along with the cost of just administering the injection and the injection to the owner or the cost to the owner that we're looking at. Are we able to safely multi-dose this drug out in practice?

Lisa Fortier: 7:17

Yeah, that's a great, great point. I'm curious from both of you. Oftentimes, when we do studies or we read studies that prove that something we do routinely walking horses for colic or whatever it is that they don't work and it's hard to even convince your own institution that the data is real. Have you had a struggle convincing your other surgeons or your anesthesia folks that in this situation, as you said, Danielle, this is not liposomal, bupivacaine is not effective.

Vanna Dickerson: 7:46

Yeah, I haven't noticed a struggle with it, yeah.

Danielle Hollenbeck: 7:52

Yeah, I think for the most part people have gotten on board. I think when we were starting enrollment in the study, it was a lot of education and getting everybody on board on the forefront of the study, just because we all kind of have the bias that we're giving this medication that works and that's why we do the studies is to actually have more objective data that says it works and we should be giving it.

Sarah Wright: 8:25

Always good to have an evidence versus evidence-based approach. We say that a lot, actually, on the podcast, and I can see Lisa laughing too, so we've talked about the importance of this study, Danielle. What are the next steps for future research, though, in this topic?

Danielle Hollenbeck: 8:46

Yeah, I think, looking into the human side of especially anesthesia, they have done a lot of studies and seems like have gotten away from using it on the human medicine side, um, because for the most part they've seen that there isn't a significant difference as well. I I think they are in a similar boat of they're using a lot of multimodal approaches for that. So I think there still may be a subset, for would this be more useful in a general practice type of setting or where we're not using those local blocks as commonly? Hickson and UGA group. They also recently published a paper on the liposomal bupivacaine and they used an electronic algometer to actually more objectively measure. So I think that would just be another objective measurement that you could do in a future study in combination with the pain scoring. But I think again, for our purposes, similar to what we were doing in real life, similar to how most people assess pain using to do so. So I think our other avenue, for I'm not sure how much more our group is going to do with it, but yeah.

Sarah Wright: 10:11

So, Vanna, AI is definitely something that's super interesting and we're kind of seeing more of it being published in the veterinary space. Do you see a role for AI in this area of research?

Vanna Dickerson: 10:21

Yeah, I think it is an interesting question and I think, you know, initially we've talked a lot about it at our institution in terms of, you know, how could it make us be more effective teachers or make things more so sorry efficient? You know, with anything that we do, I think. Specific to this, my thought would be I wonder if this eventually could turn into something that helps us with pain scoring, because really, a lot of the information that goes into these pain scaling systems, no matter which one you use, whether it's the Glasgow or another one, I mean it could easily go into an algorithm. So I wonder if you know, rather than having to have your nurses sit there and figure out the score, you know, would there be some way through electronic medical records and things like that for something to say hey, maybe you need to think about more analgesia for this patient?

Sarah Wright: 11:12

I always love the answers to that question. I think it's really fascinating. So we'll see what happens in the future. Yeah, and for those of you just joining us, we're discussing how the use of periancisional liposomal bupivacaine was not different than placebo regarding pain score or rescue analgesia, in a randomized clinical trial of 83 dogs, with our guests Vanna and Danielle.

Lisa Fortier: 11:35

Vanna, how did your previous training set you up for success in study design, as well as getting this manuscript across the line to publication?

Vanna Dickerson: 11:44

Yeah. So I was fortunate, between my internship and my residency I did a two-year research fellowship and master's program at Georgia, so and as part of that we were actually doing a lot of surgical research. So a lot of pain scoring, a lot of thinking about, you know, making sure we're doing right by those patients, and so I think by and large I got the most experience with that type of study and with really just scientific writing through that process and you know from there, I think I have a good number of publications. I think every time I go through the review process I learn how much I don't know and how much I have to learn. But it's OK, you know lifelong learning and all of that.

Sarah Wright: 12:26

So yeah, getting reviewer comments back is always humbling and educational, so we're really thankful for that. So now we're going to move on to a set of questions that's really important for our listeners. Danielle, what is one piece of information the veterinarian should know about using periancisional liposomal pivot cane regarding pain score or rescue analgesia?

Danielle Hollenbeck: 12:52

Yeah. So I think the biggest thing is following label instructions as far as not giving it to you know, animals who are nursing pregnant not giving it in an infected site. Administer that in a multi-dose fashion. I think we're not really seeing evidence that there's an increased risk of surgical site infections. Our numbers were really small but our infection rate was 6%, which is fairly standard. So I think overall it's safe to do. We just don't have a lot of evidence, at least in soft tissue surgery, that it provides a significant difference from not doing it.

Sarah Wright: 13:43

And Vanna on the other side of the relationship. What's one thing clients should know.

Vanna Dickerson: 13:48

Yeah, I think you know Danielle alluded a little bit to this earlier but our study we are very much kind of in our ivory tower right, we have anesthesiologists, we have 24, seven nearly full staffing and so you know, while we didn't necessarily find a benefit in this situation, we do have studies like the Wheeler JAVMA 2023 article that maybe suggests, in a situation where you don't have quite as much access to the full pharmacy and the anesthesiologist, you know, maybe it is more helpful. So, you know, if you have a practitioner that's using it, I wouldn't just assume that they haven't read the literature and just don't know that it doesn't work, because it may work in their situation and you know, as Danielle just mentioned, I think it does seem to at least be safe. So, I think, as always, you know, talk to your vet about analgesic options and what's best for your pet.

Lisa Fortier: 14:39

Outstanding answers and really helpful to the clinicians. As we wind down, we like to ask a little bit of a personal question. So, Danielle, we'll start with you, and Sarah and I have a hypothesis. We're doing a prospective study on the answers to this question. When you complete a puzzle, do you begin with the interior middle and maybe go by color or a shape, or do you start with the exterior border pieces or maybe a hybrid?

Danielle Hollenbeck: 15:02

Yeah, do we get to find out your hypothesis? Once I answer, I start with the corners and then the borders and then fill in from there.

Lisa Fortier: 15:12

Oh, okay, that's a new one. So we aren't that granular in our responses. We predict surgeons do exterior and medicine folks do interior, and if you're a soft tissue surgeon you get more medicine right, you get more medicine along. So sometimes you're a little more hybrid. So orthopedic surgeons are a hundred percent border, border, border.

Vanna Dickerson: 15:35

Yeah, I mean I did tell her there's only one right answer to this.

Danielle Hollenbeck: 15:39

Maybe I've missed my calling because I seem to have some orthopedic tendencies.

Vanna Dickerson: 15:45

Vanna is yours interior, then oh, absolutely not, it's only exterior.

Lisa Fortier: 15:51

All right, you blew our hypothesis. Well, we're not done yet. You know there's a standard deviation, Vanna, for you, what's your favorite animal fact?

Vanna Dickerson: 15:59

Yeah, so I did Google this because otherwise my answer would just be like anything about cats, because I'm a crazy cat lady and in that I learned that Komodo dragons can actually have like essentially virgin births. Apparently, they can fertilize their eggs and they'll be like identical twins, is essentially all identical young but it is possible for them to make babies without the boys. So I thought that was pretty fascinating.

Sarah Wright: 16:26

That's our first Komodo dragon fact actually, so we've actually got a lot of octopus facts recently and I thought you were going to say that based on our conversation before the podcast about the book.

Vanna Dickerson: 16:35

Yeah, you know, octopi are pretty cool too with the three hearts, but yeah, literally someone said that yesterday on the podcast actually is part of the response.

Sarah Wright: 16:44

So, yeah, that was pretty awesome. Thank you both Vanna and Danielle. We really appreciate you being here today, and also for sharing your research, too, with JAVMA

Vanna Dickerson: 16:52

Yeah, thanks for having us.

Sarah Wright: 16:58

Yeah, Thank you To our listeners. You can read Vanna and Danielle'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 Equal Podcasts or whatever platform you listen to.