Blocked Again? How Lorazepam May Reduce Repeat Urethral Obstructions in Male Cats

Zero re-obstructions sounds almost too good to be true, so we wanted to understand exactly how the data got there and what it means for everyday feline practice. We are joined by study author Dr. Kelly Tart to talk about a prospective, double-blinded, placebo-controlled trial evaluating lorazepam for recurrence prevention after feline urethral obstruction in male cats, one of the most common and life-threatening urinary emergencies we treat.

We start with the “why”: feline urethral obstruction can rapidly cause azotemia, hyperkalemia, acidosis, and fatal arrhythmias, and recurrence often hits within the first couple of weeks after discharge. Kelly explains the key anatomic detail that drives the whole hypothesis: the male feline penile urethra contains both smooth and skeletal muscle, and plugs often lodge distally where skeletal muscle dominates. Many past pharmacologic approaches have focused on smooth muscle pathways, which may help explain inconsistent results in recurrence studies. Lorazepam, a benzodiazepine with skeletal muscle relaxant effects, offers a mechanism that better matches where the problem happens.

We also dig into what strong evidence looks like in veterinary medicine and why prospective enrollment, standardized care, placebo control, and double blinding matter when owners and clinicians are judging outcomes in nonverbal patients. You will hear practical discharge details including timing, dosing approach, a 30-day course to cover the highest-risk window, approximate cost, and what adverse effects to monitor such as sedation and ataxia. We close with the clinical “so what”: how this could change post-obstruction management, which cats we would avoid based on prior benzodiazepine sensitivity, and the research questions this opens for lower urinary tract signs beyond true obstruction.

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JAVMA article: https://doi.org/10.2460/javma.26.01.0045

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Transcript

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Lisa Fortier 0:31

Welcome to Epic Award-winning Veterinary Vertex, the Avium Made Journal podcast where we delve into behind-the-scene look with manuscript authors. I'm editor-in-chief Lisa Fortier, joined by Associate Editor Sarah Wright. Today we're discussing how Larazzipam reduces recurrence of urethral obstruction in male cats with Kelly Turt. Kelly, thanks so much for taking time out of your busy schedule to be here with us today.

Why Urethral Obstruction Is Deadly

SPEAKER_02 0:57

Absolutely. Thank you for the invitation to speak with both you and your listeners. I'm really excited to share the results from this uh study that I was able to do and give details associated with it as well. Thank you for joining us, Kelly. Thank you.

Lisa Fortier 1:12

Kelly, for listeners, just to set the stage who may not be familiar with this condition, can you briefly explain what female, sorry, uh feline urethral obstruction is and why it's so critical such a critical issue in cats? Absolutely.

Why Lorazepam Might Work

SPEAKER_02 1:26

So I will say that feline urethral obstruction is pretty common. It's potentially a life-threatening urinary tract emergency that occurs mostly in male cats. And the cause of feline urethral obstruction can be several etiologies. Most commonly it's urethral plugs. And these urethral plugs are uh made up of uh a mixture of mucus and protein matrix and sometimes inflammatory cells, along with uh crystalline materials such as struvite. And those are what obstruct the male urethra. Now, there's other things as well, um, and these are less common, but things like Uralus or neoplasia can also cause obstruction. And where this becomes a critical issue in cats is uh that it can cause some pretty severe azotemia, uh hyperkalemia, acidosis, and really life-threatening cardiac arrhythmias. So without timely intervention, this can progress to a bladder rupture, a ural abdomen, acute kidney injury, and even death. So although we know that it is probably a multifactorial condition, it really necessitates really rapid recognition and stabilization and then hopefully prevention of reoccurrence.

Sarah Wright 2:50

So, Kelly, what originally led you to investigate Lirazepam as a potential treatment in this context?

Gold-Standard Trial Design Explained

SPEAKER_02 2:56

Yeah, that's a great question because currently there are many studies on the lots of different facets of feline urethral obstruction. Some of these studies have um answered a multitude of questions, such as underlying etiologies or prognostic indicators and various types of ways of stabilization of these patients. Um, also, there is a handful of investigators that have looked at ways to prevent reoccurrence of this life-threatening condition. And of those recurrence type of studies, there's been this broad effort to figure out why they reobstruct and then how we can prevent it. And so um, when they look at what how they or why they reobstruct, they uh these investigators have looked at urinary catheter size or how long the catheter is left in place or the duration of hospitalization. But on the other hand, the a lot of the focus has been on prevention of reoccurrence and things that have been looked at is dietary modification, environmental management, and then this range of pharmacological therapies. And a lot of these therapies, these pharmacological agents are aimed at the urethra itself with the thought of trying to decrease urethral spasms, reduce inflammation, edema. And the goal would be to improve urine outflow and then really to target those urethral muscles to assist in decreasing that likelihood of reobstruction. So studies have looked at dantroline, uh, phenoxybenzamine, uh, steroids, and in the last 10 years, prazzosin as well. And although the results have been inconsistent, really none of them have demonstrated a meaningful reduction in the recurrent rates for feline urethra obstruction. So, from an anatomic perspective, this becomes particularly interesting because the male feline penile urethra consists of both smooth and skeletal muscle. And that smooth portion is low located in the proximal portion and skeletal in the distal portion. And why that's important is because most urethral plugs lodge in the distal portion, which is dominated by that skeletal muscle. And that's where the disconnect lies because these medications that have been studied really target that adenergic receptors in the smooth muscle. And so it makes sense that maybe we're not seeing really consistent results. So that led me to come up with you know what, why don't we try to target these urethral skeletal muscles? And larzepam, which is a benzodiazepine, is very well known to act as a skeletal muscle relaxant. And so that just made a logical option, you know, in this context. Uh, and so um typically currently, as far as larzepam is concerned, really the only studies that are out there are on the use of larazzepam in um psychoactive type of uh disease processes or for behavioral uh disorders and anxiety. So it does make it a practice, people are using it for that other disease, all those other disease processes.

Lisa Fortier 6:15

I love how this uh logically makes sense, right? You you know the background, you see a knowledge gap, and then you set out to do one of the toughest studies that has the best level of evidence. So prospective, double-blinded, placebo control. Uh, can you explain to the listeners how you design that and why that design type matters? Absolutely.

SPEAKER_02 6:36

You know, I totally agree that uh a prospective, double-blinded placebo control is that kind of, you know, gold standard because it really minimizes the biases at so many different levels. You know, the prospective component of it, I really wanted to follow the patients in kind of a controlled, standardized, and structured way. And so that started with not only the enrollment, but also the consistent treatment regimens during hospitalization and then the therapy upon discharge as well. And that why we kept it double-blinded is this meant then that clinicians, technicians, and even owners did not know if they were getting the study drug or the placebo. And so what that does is it removes that kind of unconscious bias bias when we're trying to assess the patient's response. You know, our patients don't talk to us, so we really have to use um real good uh uh uh evaluation skills from the owners and our technicians. Uh, and then that with the placebo control, it just gives us that baseline so we get a real true comparison and more reliable data. Um, as far and so that it hopefully helps, you know, prevent any other type of confounding factors in our results. The downside of the prospective study is it takes a long time to uh to do these studies. So for me, this study it took six years um to enroll our patients. Uh luckily I had two excellent dedicated ECC residents that helped me gather these patients and also uh to to make these phone calls and really obtain a trustworthy conclusion.

Sarah Wright 8:25

Yeah, it sounds like you had a great team to make this happen. I for sure did. So, Kelly, you specifically excluded cats with Uralus and urinary tract infections. What was the reasoning behind that decision?

Discharge Plan Dosing And Cost

SPEAKER_02 8:37

Yeah, we did exclude those specific conditions. And the reason why we did that is because both of those conditions can either mimic very similar clinical signs, similar to feline urethra obstruction, or they can even actually cause like urolis can even cause feline urethra obstruction. So our, you know, our clinical clect, really clinical question that we were trying to answer was to determine ways to reduce the recurrence of the most common type of feline urethra obstruction, that is with the urethral plug. Therefore, we had to remove these other causes in order to keep our data really clean. And we did that by um we did all our patients had urine cultures to rule out uh potential UTIs. Similarly, we also did abdominal radiographs looking uh that were reviewed by radiologists to rule out making sure there were no urolyss and that neoplasia also was not, you know, on that possibility for those uh presenting signs on those patients.

Lisa Fortier 9:41

For clinicians that haven't gotten to try this yet, Kelly, what is a treatment protocol and maybe even the cost look like for these cats after hospitalization?

Zero Recurrences And What It Means

SPEAKER_02 9:49

Yeah, that's a great question. So um all of our patients were discharged with either Lorazepam's either Larazzepam study drug or the placebo study drug. And they we went out for 30 days. Uh and they also were uh prescribed a um HILLS CD multicare or a prescription urinary tract diet. They also went home with um analgesics, buprenorphine, and gabapentin um for both analgesia and then an exidiolytic. And uh I will say that uh we chose to use 30 days as our our studied time frame with that drug with Lorazipam and the placebo was because what we know is that 60% of feline obstructive patients uh have a recurrence within the first 15 to 17 days. So we really wanted to bridge that entire time frame that we would be concerned about. As far as the cost, I will say at this time um lorazipam is relatively inexpensive as an oral medication. Uh I uh I will tell you that our patients um about a 30-day uh a 30-day trial vial was about$30 for the donors. Yeah. So at this point, I I I'm not sure what will happen going forward, but at this point, it seems to be pretty inexpensive. Yeah. Oh yeah, a heck of a lot cheaper than a PU surgery for uh amen. Amen to that for sure, for sure.

Sarah Wright 11:36

Yes, study really has the potential to be a game changer, and the headline is striking zero recurrences in the Larazopam group. What was your reaction when you saw that data?

SPEAKER_02 11:46

Yeah, I'm not gonna lie, I was very surprised and really happy to see the results. I mean, it's even possible I did a, you know, a little happy dance in my office when I we got those results. But, you know, honestly, given the long study duration, I really had no idea where the results were trending. Um, I did know that we had reoccurrences, but I didn't know if they were in the placebo group or the larazopam group. Um, and so uh it wasn't really until we unblinded every, you know, once the study was done and we unblinded the results that we were able to notice these really positive results.

Lisa Fortier 12:29

As Sarah just said, uh Kelly, there was 0% recurrence, which is amazing in the Larazzipam group, and then 16% in the placebo group. Uh, what's a clinical, I mean, that seems obvious, but uh is that a statistical, clinically significant difference?

SPEAKER_02 12:45

Yeah, that's that's a great question. So it is statistically significant, um, zero recurrence rate versus 16%. Um, I will tell you that uh in in those studies that have done the uh a lot of these other uh looking for re at recurrence rates in feline urethra obstruction, they there's a pretty big range of recurrence. And some studies are as low as 18%, and some have gone up to 66%. And so it depends on the study, the style, you know, the patient population, a number of factors that could make that huge, wide range for recurrence. I would say the majority of the studies tend to cluster closer to 20 to 25 percent recurrence. So yes, 0% was pretty remarkable, remarkable. Um, and even our placebo group had a 16%, which falls in lower than, you know, the average, if you I guess would call it. You know, I the reason behind that that we feel that could be due to is really of that multimodal approach that we used for all of our patients. Uh, you know, not only analgesics and anxidiolytics, but we also they were all on prescription diets. Yeah. Uh, and so I really think that helped as well. Uh, that and that may certainly have influenced why we had a you know a lower reoccurrence rate, even in our placebo group as well.

Lisa Fortier 14:17

Sure.

Sarah Wright 14:18

So you also tracked lower urinary tract signs. What did you find there and why does that matter clinically?

SPEAKER_02 14:24

Yeah, so lower urinary tract signs, you know, have been reported to occur, especially uh after those first few weeks, couple weeks post-discharge. And, you know, and actually it that makes sense. And uh and the reason is is because we think that these lower urinary tract signs continue, is because there's you know, urethral irritation secondary to recent catheter removal or maybe even some persistent ongoing inflammation post-retropulsion. So again, it it makes sense that if we were going to track reoccurrence rate, we'd also see, you know, could we help out? And could this drug be helpful uh at that, you know, by targeting that skeletal muscle relaxation even during this recovery period? And what we did find is that the cats and that Larazopram group actually did overall show low less lower urinary tract signs than in comparison to our placebo group. But I will say that it that did not reach statistical significance, but from a clinical standpoint, that trend is still quite meaningful. And you know, sending a cat home and having that's been previously obstructed and having them experience less straining or vocalization and uh it is really beneficial not only for that patient, but also for the owner, especially after they've, you know, probably have themselves, the owners had a pretty stressful event and costly event as well. So so I think you know, it it does taking this one step further, it just does it, it raises like some interesting questions like could Loraze Pam have a role in cats even presenting to their referring vets restraining secondary to non-obstructive feline lower urinary tract diseases? You know, who knows? Um, you know, and hopefully future studies would really help answer these questions.

Lisa Fortier 16:26

Kelly, you opened by saying it's not a commonly used drug. So uh what side effects did you see and what should veterinarians be vigilant for?

SPEAKER_02 16:36

Yes, absolutely. So there, like I was mentioning, there are limited studies on larazzepam, and these again are typically behavioral studies. Um, and surprisingly, there was that these studies have reported very minimal side effects. However, it it would make sense that potentially larazocam, larazpam could cause potential adverse effects just associated with the mechanism of action. I mean, it is a benzodiazepine, and we know that benzodiazepine can cause sedation, ataxia, in some patients, increased vocalization and even increased appetite. So those were really the four things that we we tracked and that we wanted to look for. And so we, when we called these owners, or uh, I will say that there was a very specific set of questions that we inquired about all four of these possible side effects. And of the 34 cats in our Lorazopam group, they um four of them uh showed some mild ataxia, eight of them showed mild sedation, five of them had an increased appetite, and four of them had increased vocalization. So again, keep in mind that we had to uh hopefully we didn't lead owners into a, you know, because some loans are like, well, what's ataxia? You know, we'd have to use that definition of, well, they're just stumbling on their feet, you know, do they, you know, and and and so uh hopefully we were able to really pinpoint that down um as far as what those side effects could have looked like. Now, I will have to admit though, our challenge was is that not only did we send these patients home with Lorazopane, but even in the placebo group, those patients, we all of our patients had buprenorphine and gabapentin, which cause sedation and ataxia. So it really, it kind of, you know, it it could be, it could have to potentially been some type of a confounding type of uh result uh from what owners were reporting. So again, it's just difficult to truly say. Now, I will tell you that my residents who are speaking to these owners on day 7, 15, and 30, um, and explaining and talking about these side effects from what both of them have told me is that it really did not appear to be clinically significant or really troubling from the owner's perspective. So if you weigh these potential side effects against the benefits that we really saw in the Lorazopram group, it's pretty clear that owners felt the positives outweighed the downsides.

How This Could Change Practice

Sarah Wright 19:29

Yeah, very good disclaimer to have. Yeah, absolutely. So, Kelly, based on your findings, how might this change the way veterinarians manage cats after a first urethral obstruction?

SPEAKER_02 19:39

Yeah, so it is, it's we we again, as I've said probably a couple of times, it's it is pretty compelling evidence that this could be beneficial in these patients, not only to help prevent the recurrence, but also maybe even potentially these lower urinary tract signs that could be seen after discharge. So I'm hopeful that clinicians will consider using larzepam, you know, as part of their discharge treatment regime. And we started, and I will say that we did start uh Larazzipam in hospital as soon as the patient was amenable to eating. And in some patients, that was as soon as eight hours afterwards, up to potentially, you know, a day later, and then obviously all certainly at home as well. Um, we what we did uh we used our dosing, we used a half of a 0.5 milligram tablet, which ended up being about basically 0.25 megs per cat. And we use that twice a day. Now, the dose range, if you look up the dose range, is pretty um is pretty variable. Um, and so, and also as you can imagine, we couldn't control the weights of our cats. So some cats, you know, had a lower milligram per kilogram, actually as low as 0.025 megs per keg. And some had all the way up to you know 0.08 or 0.08 megs per keg. So there's there's a quite a bit of variation, and I said that in reverse, but uh, but it was really they're well tolerated. Uh, and and the dose that we use is um has been used by most is what was used for most behavioralists. Uh and then the buprenorphine and gabapentin, we had both of those were um only for five days.

Which Cats To Avoid Lorazepam

Lisa Fortier 21:32

Are there any patients, Kelly, that you would avoid the use of Lurazepamin when they're obstructed?

One Takeaway And Closing Notes

SPEAKER_02 21:38

Yeah, that's a great question. Thank you for bringing that up. Um, so I will say that um there are there is um patients, and I and I I've been doing this for 30 years, uh, you know, on the clinical floor, as I'm sure your listeners are have lots of experience. When a lot of times when we're up on Obstructing these patients or doing the retropulsion component of it. If we're using benzodiazepine as part of our sedative type of uh regime for this retropulsion technique, um, there are some patients that we've seen that are what after getting a benzodiazepine are um either difficult to stay down or have uh are hallucinatory or seem to have a difficulty time recovering, those are patients that I know that we have said, Oh, I wonder if they were sensitive to the benzodiazepines. So as a clinician, and really as uh what I would recommend is if you see any of that type of uh behavior or um changes during your sedative process, I would not recommend using larzepine just to be safe.

Sarah Wright 22:52

So now to our most important question of the podcast, Kelly, if you had to give one takeaway message to clinicians, what would it be?

SPEAKER_02 23:01

Yeah. So my main takeaway is that larazzepan looks like a promising, safe, and well-tolerated option to reduce the recurrence of feline urethra obstruction. And really, since we saw this 0% recurrence rate in the larazzepam groom, this really suggests that targeting that skeletal muscle relaxation and stress is an important piece of the puzzle. And I really hope that helps our patients going forward and also opens up the door to lots of some lots of studies to give us more answers about this, about this medication.

Lisa Fortier 23:36

Kelly, thanks so much for sharing this really groundbreaking information with us, Jabman, and for putting together a fantastic study. The time is well worth it, I hope, for our feline patients.

SPEAKER_02 23:47

Thank you. And thank you so much for having me. I really appreciate it. I love sharing this information, and I hope that it helps a lot of our feline urethral obstruction patients going forward.

Lisa Fortier 23:59

For our listeners and viewers, you can read Kelly's article in JAVMA. I'm Lisa Fordier here with Sarah Wright. Be sure to tune in next week for another episode of Veterinary Vertex. And don't forget to leave us a rating and review on Apple Podcasts or wherever you listen.