Well, welcome everybody to this webinar, which I've called the ins and outs of using opioids in Cats. It seems like a very popular topic, cause cats, as we know, are unique and don't follow the rules of all the other species that we work with. And so, I'm Sheila Robertson and I am a trained anesthesiologist and also trained in, in pain management.
And I currently work for a company called Lap of Love. Veterinary hospice, so we do a lot of end of life care, but I am still associated with the University of Florida. So let's figure out what we're gonna talk about today and involving opioids.
So I'm gonna talk about their role in acute pain management, cause that's really where they play a role in our patients. We don't use opioids very often for chronic pain in cats or in dogs. I'm going to talk about terminology because a lot of people get confused with the terminology about the different drugs.
I'm going to talk about the different types of receptors and obviously which drugs work at different receptors and what they do. Obviously talk about side effects because we always want to aim for what we're looking for, which in this case is good analgesia but without a lot of side effects. And then I'm gonna finish up a little bit on like what to use and when, and I have a couple of little cases to share with you.
So the first thing we're gonna get some terminology out of the way. And multimodal analgesia really means that what we're doing is that we're using several different drugs that have different modes of action, so they work at different parts of what we would call the pain pathway. So that's what multimodal means.
And although we're focused on talking about opioids today, We must remember that usually they are used in combination with other drugs in a multimodal fashion. And the most common combination for acute pain management would be an opioid plus a non-steroidal. And we're just illustrating here that they work better with a friend.
So the two together are gonna give you a very, very good outcome, but we will be focusing on how we use the opioids. Another term that's important to understand is a term called preventive analgesia. Sometimes it's called pre preemptive analgesia, but this means about the timing of when you give your drugs.
And with the opioids, there is a lot of benefit, a huge benefit of giving your opioids prior to The pain occurring. So when you can plan that, that's giving your opioid before you actually start the surgery or if it's a trauma case, you want to give your opioid as soon as possible after you actually get the cat into your clinic. So we've, we know that if we can get the opioids on board, we can actually prevent a lot of the wind up in central sensitization that can occur if we don't treat pain robustly and quickly when we see it.
Now, the thing that's really interesting about opioids, and I've certainly been working with cats and been in the anaesthesia and veterinary world for over 40 years now. And when I first started, it was almost like we don't use opioids and cats, and we certainly don't use morphine. And I was like, well, why?
And so the whole story is all about this urban legend now called morphine mania. And if you look at when these reports were coming out in the 1800s, the early 1900s, and even as late as 1957, they would say that when you gave opioids, and they were talking mostly about morphine, which was the one drug that was available in humans and for, for use. They would say that if you give it to a cat, they would, you know, dart around the room, explosive impulsivity, they'd stop, start suddenly jumping abruptly.
So basically this was called morphine mania and unfortunately, it kind of really delayed the use of using opioids for clinical effect in cats. But when you look into stories like this, it's always good to find out like what's really going on. So I actually looked into it.
And if you look back at those really, really old studies, they were using 20 milligrammes per kilo of morphine. And all of you listening know that that is like, you know, 20 times or more than what we now know is the clinically effective dose. So it was really, now is an urban legend.
And so what we found was that as soon as we figured out that those were really ridiculous doses to be using. And no wonder we were seeing side effects that we didn't like. Once you look at a pub med search and I looked for opioid, opiate cat, feline, you can see that once that opioid mania, story was, was demystified, you can see that we started seeing, you know, in the, you know, 1960s, a lot of information coming out and being published in peer-reviewed journals about the use of opioids in, in cats.
So, the World Small Animal Veterinary Association, they have a list of essential medicines for cats and dogs, and opioids are in that list of core essential medicines. But we also know that some of our colleagues that work in certain countries don't actually have access or easy access to opioids to help their feline patients, but it is considered, all the opioids that, that, most of you listening to have access to are considered essential medicines. Now, this is probably one of the key resources that I am going to send you to.
This is the 2022 International Society of Feline Medicine guidelines on the management of acute pain in cats, and it is completely open access, free for anyone to download, and I've put the QR code up on the screen and also the, the reference that's in the Journal of feline medicine and Surgery. And clearly there's a lot of interest in, in acute pain management in cats cause I looked at the downloads and, you know, almost 91,000 people have downloaded this document. So this is, even though I might mention certain doses and drugs.
Today, this is where I'm gonna send you to get key information on doses duration of effect and also it helps you this, this paper talks about how you create a plan, how, how you use all the different drugs in, in combination. So, definitely download this article. So terminology, opiates are derived from opium, which is the poppy seed.
And that's a term that, you know, has been used. The better term, as I've been using already is an opioid, and they're not necessarily derived from opium itself, but all of the opioid drugs interact at opioid receptors. And so that's the term that I think is easiest to use.
So I refer to all of the drugs that we're going to talk about as being opioids cause they interact at at this receptor that we're really interested in. The word narcotic is really not used at all to describe this group of drugs, cause it really means, it's really a legal term and it infers, you know, abuse, addiction, a criminality. So we don't use the term narcotic in relationship to this group of drugs anymore.
And then we're going to talk about the receptors because there are certainly multiple receptors. So we have the mu, k Kappa, and delta, and those are still very, very accepted terms, but you will see in some of the maybe newer papers. That the new receptor, which is the one where we'll talk about like that's where morphine works, is often called the OP3 or the MOP receptor now, and that's just different classification.
But we're gonna use the, you know, the original terms, new, kappa, and delta, and the ones that we're really gonna focus on for being clinically relevant are the new and the kappa receptors. And I think it's, it's important to understand that all of the mammals that we work with, and we're talking specifically about cats, there is an endogenous opioid system that exists within the the species we work with. So cats have opioid receptors and we have opioid receptors, and there are endogenous receptors in the body that act and interact with these receptors, so we have things like beta endorphin that works at the new receptor, we have diorphin that works at the kappa receptor and then kephalins at the delta receptor.
So there's clearly a reason why we have this built-in system and endogenous products that can interact and cause analgesia. So, obviously a very, very important system within the body, probably created for self-preservation and to help with analgesia. And then we're gonna talk about the exogenous drugs, the exogenous opioids that we use to target those receptors.
And the opioids that we use are classified into different terminology. So we have agonists, we have partial agonists, and then we have agonist antagonists, and then we have a group of drugs called antagonists. And this is a little bit confusing for some people like what drug, you know, is morphine, what, what is it?
Is it an agonist, is it a partial agonist? And I'm gonna work through all that and explain, you know, what the difference between these terms actually are. So, classification of the opioids, if we look at agonists, we see this list that we have here that you're all probably very familiar with fentan fentanyl, hydromorphone used a lot more in North America than in, in Europe, but peridine or Demerol, methadone, morphine, which is probably still the gold standard that we compare things to and oxymorphone.
So those drugs are agonists at the new receptor, and they also work at the kappa receptor. Then we have the partial agonist, and the main one or really the only one that we have in veterinary medicine, and it's used a lot in humans too, is buprenorphine, and it works as a partial agonist at the new receptor and produces analgesia. And then it's a little controversial what it does at the Kappa receptor, but it's probably a partial agonist, maybe a weak antagonist, but it's main action and what we're looking for is its effect at the new receptor.
And then we have butorphenol, which is an agonist antagonist. So it actually doesn't have a positive effect at the new receptor. It actually antagonises that, but where it exerts its effect is that the kappa receptor and that's why it has a very, very different profile and we'll talk about its profile.
And then we have the pure antagonists, so those, the ones we probably know a lot about are naloxone or naltrexone. So they have no effect at the new receptor and they have no effect at the Kappa receptor. So they don't produce any analgesia, but we'll talk about what they actually do in a moment.
So when we're looking and now we've described that we have receptors, and then we have drugs that we can target those receptors with, it's all about a lock and key mechanism, how that drug and the receptor fit together, and what does that activate in the body? Does it activate a good thing? And what we're always looking for obviously is for analgesia with with these.
So if we look at this schematic, if we have a naive patient, so they have, they're sitting in front of us and they haven't had an opioid, and so they've got a lot of empty opioid receptors. And if we give them an agonist drug, and for example, that's morphine, the morphine will then go into that opioid receptor and it fits really, really well. So we call that a full agonist and it generates an effect.
And what we're looking for is, is analgesia. There are some other side effects that we'll talk about. But then we take a drug like buprenorphine, which is a partial agonist, so it doesn't fit completely into that lock and key mechanism.
It partially fits in there and it does generate an effect, but it's a limited effect. And then we have our naloxone, which is an antagonist. So it actually just blocks off that receptor.
It doesn't actually exert any analgesic effect in the animal, so it blocks the effect of other opioids that we might give. But We can also use these drugs to reverse an opioid like morphine that's already in that receptor. So sometimes we use naloxone to reverse if we're in trouble for some reason, which is very rare because opioids are very safe and easy to use in cats.
But if we needed to reverse, we would use something like naloxone to knock the morphine off that receptor and restore us back to baseline. So the opioid receptors, we always think about them as being in the central nervous system, so in, in the brain and in the spinal cord, but they're found all over their body and they're found in a lot of peripheral sites, including the gastrointestinal tract, and that's why we sometimes see adverse side effects with opioids. We see things like ileus decrease motility.
But they're present in the skin, they're present in synoval membrane of joints, and if you have an inflamed tissue either in a joint or inflamed at a surgical site, we actually have opioid receptors there that actually get up regulated and so sometimes rarely in cats, we can target those inflammatory up regulated opioid receptors in a joint and actually inject an opioid into a joint and achieve analgesia. So let's look at opioid receptor drug interactions. So if we take a drug like fentanyl and it's a full new agonist, what we see is we get a dose response.
So the effect that we're looking for is analgesia, and what we see is the more we give, the more we actually get more analgesia we get and eventually we're gonna reach a maximum effect. So this is what a dose response curve looks like for a full m agonist like fentanyl or morphine would would have a dose response curve that looks like this. Now, a lot of people get a little bit confused with what we call efficacy and potency.
So, potency is really just about how much drug that you actually need to elicit a response. So we could have 2 different drugs here. So we have fentanyl and we have morphine.
And fentanyl is a lot more potent than morphine. So we have to give not very much fentanyl to reach that maximum effect. But morphine, although it's less potent, if we give enough of it, we can reach a maximum effect.
So, It's not as potent, but it's just as efficacious. And as you can see, the dose of morphine to reach that peak effect is higher, like 100 times higher than fentanyl. So that's the explanation of, of potency.
And then we have our partial agonist, so the, the one that we use a lot in medicine is buprenorphine. So what we see with buprenorphine is, it's the dotted line. So it's quite a potent drug, so we don't need high doses on a milligramme per kilo basis to get what we want, but it does, because of its partial agonist activity, it reaches a ceiling effect.
And then if we compare it to morphine, morphine is, is less potent, you need more of it to reach a maximum effect on a milligramme per kilo. Low basis, but we can reach a greater maximum effect with the, the morphine and fentanyl compared to buprenorphine. So we call this a ceiling effect, but clinically, when we look at all the data on buprenorphine, we actually find that the doses we're using, we're getting some very, very good analgesia.
And, you know, the ceiling effect is, is there, but for certain types of procedures, for example, soft tissue surgery, we are getting, you know, the effect that we need for that cat. So then we have the agonist antagonist, and really the main one that we have in veterinary medicine is butorphrenol. So as we already said, it is an antagonist at the new receptor and works only really as an agonist at the Kappa receptor.
So it, it has very limited and short lasting analgesia. And the thing that we need to understand about bearphenol is that it doesn't really have a dose response curve, like, if you give morphine or fentanyl, if you give more, you'll get more analgesia, to, to meet the, the patient's requirements. But I did a study, on, on this, many, many years ago now, and we looked at 0.1, 0.2, 0.4, and 0.8.
And really, there's no benefit of giving high doses of petrophenol because you've already reached its maximum effect, and we found like at about 0.2, you're already at the maximum effect and giving more doesn't give you more analgesia, it just gives you more side effects. So it truly has a ceiling effect.
And we only use bitrophreal for, you know, pretty minor procedures, and we'll talk about that towards the end of the webinar. So, I think it might be a little bit interesting just to spend a moment or two on how did we figure out which opioids worked best in cats, because most of you now know we have opioids that are labelled for use in cats. But how we got there is a long story, a lot of history.
And I'm only going to spend a moment on this, but I think people should understand all the work that goes into creating these drugs that come to market, that have a label, yes, you can use this opioid in a cat. So what we actually did was we looked for a pain model because with a pain model we have a uniform population of animals, we have a consistent controlled stimulus, so we can look at a drug and get a lot of information about that drug, and that then helps us move that data into the clinical arena. And so, but in clinical arena, when we're talking about clinical pain, it's a very diverse population, different types of pain, source, cause, duration, and unless we have some good data and good doses to enter into the clinical arena, then we're just like guessing at what a cat might need to treat its, it's pain.
So the model that we actually use, and I did a lot of work with people like Polly Taylor, Doctor Duncan Lasals, we worked at Cambridge, we worked here at the University of Florida. And what we do know is that thermal threshold testing is a very, very effective way of looking at how opioids work. So basically, you can see these cats are pretty relaxed, they're wearing a little a little jacket.
And underneath that jacket is a probe that we press a little button and that will start to heat. And when the cats have no opioids on board, they will suddenly like turn and look at the probe and flinch, and we of course, turn it off so we don't hurt them. And then we give an opioid and what we can measure is how much more heat that they will tolerate.
So it's like, you know, looking as a surrogate marker for antinociception or analgesia. So that's the model that we used. And with that model, we actually went through multiple, multiple drugs, lots and lots of different opioids in cats.
And then what we were able to do with that is work out a dose to take into the clinic, what was the best route of administration. When we give it, how fast does it actually take effect? How long does it last, you know, what's the magnitude of the effect?
Is it really a great opioid analgesic? And then, of course, we saw some of the adverse effects that we can report. So with studies like this, what we were able to do was we were actually collecting blood samples to look at plasma concentrations of fentanyl, but looking at how much antinoysection, how much it allowed us to raise that thermal threshold that the cats didn't care, that the probe was getting hot.
And so from this data, we were able to actually show that as long as you kept the plasma concentration of fentanyl above, we've got here 1.07 nanograms per mL, they were analgesic in using our clinical model. But that data then helped people then look at clinical scenarios.
So looking at that data and creating, you know, what's the best infusion rate for analgesia or you know, in cats using fentanyl. So this was a study that was published, you know, after our study. So a loading dose of 5 mics per kg IV and then you start your infusion, which is 5 mics per kg per hour.
And this study was done in a weight cast and it was really very reassuring to, to see that they their results were very similar to us. As long as the plasma levels were over a certain number, then the cats were not responding to the thermal threshold, it's the same model. So this allowed us to kind of really create tools or protocols to take into the clinic.
Now, talking about the use of things like Fentyl and fentanyl infusions, a lot of you are probably doing some pretty complex anaesthetics and for, you know, major procedures in cats, and a lot of us will run opioid infusions and other drugs we run as infusions. To allow us to turn the vaporizer down cause the inhalant anaesthetics are the, the one drug that causes us a lot of problems. They cause respiratory depression, they cause cardiac depression, they cause low blood pressure.
So we usually try and give something to the animal so we can turn the vaporizer down and all of those things are, are much better. They have better blood pressure, they breathe better. So, we often have used opioids to decrease the amount of inhalant agent that we need, so either isofluor or sevoflurane.
So when we look at the difference between dogs and cats, it's remarkable. Like we know that fentanyl infusions can be analgesic in cats and provide them excellent analgesia. But when we use them to try and turn down the vaporizer, the effect is completely different from the dog.
So if you were running a a fentanyl infusion in a dog, you should be able to turn your vaporizr probably down by about 50%. But when we run a fentanyl infusion in cats, the ability to turn down the vaporir is really minimal. And we think that's because the opioids seem to actually cause some sympathetic stimulation in cats, so they, they work quite differently than they do in the dog.
So if you're running a dog and you always know you can turn your vaporizer down, when you are running a cat on a, on an opioid infusion, you need to be checking the depth of anaesthesia and you'll find you cannot turn that vaporizer down as much. And this holds true across all of the opioids. If we look at buprenorphine, given prior to a surgical procedure in cats, it's only about 14% anaesthetic sparing, but if we look at dogs, up to 35% anaesthetic sparing.
So this is again, why we talk about cats as being very, very unique in respect to a lot of drugs including the opioids. Now, does the route of administration matter? And although a lot of people in Europe aren't using hydromorphone, it's a drug that's used very, very commonly in, in North America.
And so this is a study that we did looking at hydromorphone, but giving it IV IM or subcutaneously. And what we found was that the best route of administration for this drug was to give it intravenously. So when we give it intravenously, it goes into the blood and it's at very high levels and it gets transported down a a gradient into the brain where it's going to be doing its attachment to the opioid receptors and creating that analgesia.
So it works very, very quickly. What we saw was we got excellent thermal thresholds, so good antinociception. And the duration of effect was the longest compared to IM and sub Q.
So what it was doing was going IV, driving it down a gradient into the brain where it attached to those opioid receptors for a long time. I am. As you'd expect, it was a longer onset to peak effect, wasn't as good a peak effect, didn't last as long, and subcutaneous for this drug is definitely not what I'd recommend.
It took a long time to reach peak effect. It didn't last very long, and then there were some adverse effects from the subcutaneous route that we will talk about. So when we talk about opioids or any analgesic drug, a lot of people say, well, I gave this really good drug and I gave it at the recommended dose.
But that doesn't mean to say that it worked. So we always, always have to have an outcome measure. So unless we have an outcome measure, we cannot claim that the drug we gave to the cat actually worked.
So what does pain management success look like? So we have to have an assessment tool, and the one I'm going to mention today that a lot of people are now using is the feline grimace scale, and you can download this onto your smartphone. And and use this.
And what it does is it looks at the facial action units in in the cat. And they're correlated to the severity of pain. So we're looking at ears, eyes, the muzzle, the whiskers, and where the head is, and it's scored from 01 to 2, so the most a cat could get, and that would be a very painful cat, would be 10.
And the creators of this tool, Paulo Steigal's group, recommend that at a score of above 4, we should probably rescue that cat. So here's a picture of a cat that has a pretty high score. We can look at the, the ears, the eyes, where its head is, it's muzzle.
You can actually see this cat is, if you click, carefully, it's salivating cause it feels pretty unpleasant because of the pain, and we're looking at the whiskers. Now, when I gave or we gave that cat an opioid, this is a picture that Doctor Seagal shared with me. You can see the immediate transformation in that cat.
The ears pop up, the eyes open up wide, and you can see the big dilated pupils that we'll talk about. Classic side effect of opioids in cats. The cat's mouth is now relaxed and the whiskers are relaxed.
So that is our outcome measure. So clearly the opioid we gave this cat. Worked because she now has a pain score of 0 or 1 out of 10, whereas before she had a very high score.
The reason I'm, I'm recommending the feline grimace scale is it's very easy to use and cat owners can use this. So when you want to discharge a cat home, but you want the owners to be able to know if the cat is comfortable or not, you can have them download this app onto their phone, they can check their cat and report back to you whether or not your treatment. In the home environment, once they've left your clinic, is actually working.
So we talked about the clinical classic side effect of opioids in cats, and one of them is madriasis. So that's just the big dilated pupils. And that's pretty unique because in in other species, including ourselves, if we get an opioid, we get pinpoint pupils or meiosis.
So sometimes people claim, and it's true that when a cat has an opioid on board and you approach it, they get a little jumpy or they're in their cage and they're coming towards the front of the cage and they bump into the cage and they kind of jump back and they startle themselves. Well, it's because, you know, just imagine this cat's looking at you. And are looking at, looking at this group of surgeons here, when their pupils are dilated, they can't accommodate very well.
So everything is a little bit blurry and their depth perception is, is really abnormal. Think about yourself when you go to get an eye test, and they dilate your pupils. You can't really, read something close up.
So this is what happens to cats. The other thing is, bright light is very, very unpleasant to them when they have dilated pupils. So basically, we need to have glasses, right?
When they're under the influence of, of opioids, but not a lot of cats are going to wear, wear the the sunglasses like we do when we come out of our eye appointment. So in recovery, obviously a quiet area, but when their pupils are dilated, you want to dim the lights. In this case, they've dimmed the lights and put a cover over the the cage.
And then when they get home, what you want to do is advise the owner, while their pupils are dilated, that they should go in a nice room with the shades turned down, and, and no bright lights, until the opioid madriasis has, worn off. The other side effect, and it's not an adverse side effect, it is a side effect that we talk about in cats is most cats get very, very euphoric. So this is like they paddle with their feet, they roll around, they purr.
This cat actually had an excruciatingly painful corneal laceration when it came into the clinic, we gave her opioids. And then she was a lot more comfortable, had a much better pain score, but you can see that she got quite happy on her opioids. Here's a cat that has gone home with an opioids, and it's buprenorphine still on board, and you need to discuss the fact that They're going to behave with an op board with the caregivers or owners, because here's this cat that's gone home.
He had actually had a nucleation. He had a cleft palate, but you can see he's making the muffins, paddling with his paws, he's rolling around. I don't have the audio turned on here, but he's like.
He's just rolling around, so he is very, very euphoric, and that's not an adverse side effect. So that is something you need to warn owners about that your cat is going to have these behaviours, and it's all normal and expected because it's due to the opioid drug that we've given him or her for her pain management. But one of the adverse effects that we don't like is nausea and vomiting, and that's commonly associated with morphine and hydromorphone.
And so you can see the cat on in the picture here clearly got an opioid with the big dilated pupils, but you can see how she's like very nauseous, she's like got, you know. A lot of salivation going on there and she'd actually vomited just before I took this picture. So there are some drugs that we choose to avoid, often morphine because of the nausea and vomiting, it can cause.
But it's not all about just the drug, it's the route of administration and going back. The hydromorphone data, what we found was that the IV was the best route as far as onset, duration, intensity. But when we gave it IV we saw no vomiting and nausea in our research cats.
But when we gave IM, half of them looked, you know, not very happy. They were vomiting and salivating. But when we gave it sub Q, all of them were extremely nauseous.
So it seems to be related to the how quickly the opioid light hits the emetic centre in the brain, and then when it hits it, you know, like overwhelms it with the IV root, it actually shuts down the vomiting centre. But if it's trickling in like with the sub Q, it actually stimulates the vomiting centre. So it's not just about the drug, it's how we give it.
So clearly hydromorphone, other than given by the IV root, it is, as you might be able to tell, not one of my favourite opioids in, in cats. And then we have another pretty unique event that happens with cats, and that's opioid-related hyperthermia. So they can get hot after we give them an opioid, and that's pretty different from the other species that tend to actually either stay normalthermic or actually get hypo drop their body temperature with an opioid.
So this hyperthermia, which if we define it as a rectal temperature above 90 39.4, is reported with multiple opioids. There's like 3 or 4 publications, and it's often mild and it's often self-limiting.
Like it'll go away within 1 to 4 hours of giving the opioid, but I have a little asterisk here because we have a high dose buprenorphine in the United States. And when they're, it lasts 24 hours, and so they're usually have elevated body temperatures during that entire time. So hydromorphone is the drug that we have data on.
That it, it happens nearly every time you give hydromorphone to a cat at an analgesic dose, they will get a high rectal temperature and it can be very severe. I've seen it them go up as high as 42.5.
That is hot and I've actually had cats like actually pant when they've been given hydromorphone. And so sometimes the opioid-related hyperthermia. May need intervention, like we have to put a fan, cool water on their feet, and very occasionally maybe reverse that opioid if they're getting, you know, way up into the, you know, 42.5.
So, but with the other ones that we're using more often, buprenorphine, methadone, usually you will see the elevated temperature, but it's self-limiting. Another little fact that we've seen and it's been published is that if they go into surgery with an opioid on board and they get very, very cold when they come out and start warming up. The colder they are at the time of recovery, the more they have a greater rebound hyperthermia.
So that's another good reason to keep cats nice and warm during the procedure, so they don't like overshoot a lot with their rebound hyperthermia. The reason we think this happens in cats is that the opioids seem to actually reset the hypothalamic thermostat in cats. And so it's an altered, it alters their ability to thermoregulate and it just resets it and that's why we see these high temperatures postoperatively or post-ration.
And then there's some interesting things on, obviously, we're using opioids in, in kittens, we're using them on adult cats, and there was this nice paper by Brad Simon looking at, you know, is there a difference in the efficacy of opioids at different ages of cats. And this is a North American study, so it was done with hydromorphone. They looked at cats aged 6 months, 9 months and adult cats, and what they found was that there was actually a difference in the younger cats, the duration of hydromorphone was shorter and it didn't have such wasn't as efficacious, but this just really reinstates that you need to be doing an outcome measure.
Because although yes, in younger cats, you may have to doze this drug more often, you're gonna be setting up your redosing or your administration protocol based on your pain assessment. So let's look at the opioid agonists in a little bit more detail, and there's a lot of them that we're going to, that on this slide, but I'm just going to actually focus on the ones that I think have the best clinical utility. So we've already talked about fentanyl, so we're now gonna focus on methadone.
And so, methadone is perhaps maybe my number one. Opioid for dogs and cats, but certainly in the cat world, when I have access to it, and unfortunately in the United States, we don't have a, veterinary labelled, methadone for use in cats or dogs. Canada does.
I know most European countries do, the UK for sure, but it is something that is, it's a very, very different opioid. And the reason it's different is, although it is a pure new opioid receptor, so it has that really great dose response, fits really well into the receptors that provide the analgesia, the new receptor. It works at another receptor.
It works at the NMDA receptor, and the NMDA receptor is very, very important. It's found in the dorsal horn of the central of the spinal cord. And when we do surgery or the cat has had trauma, what happens is when pain is being transmitted from the periphery to the spinal cord, it will actually up regulate the NMDA receptors and that causes central sensitization or some people call it wind up pain.
And so if we can protect that or stop that happening. Then it's very, very beneficial. And what we know is that methadone works both at the opioid receptors, but it works at this very specific NMDA receptor as well.
So is methadone the most versatile opioid? In my book, yes, it is. So it has what we call dual action, those two different receptors.
I have yet to see a cat actually vomit with methadone. The hyperthermia, if you see it at all, it's very, very mild, so we don't have that issue. Usually they get pretty happy on this drug, and it can be given IV, it can be given IM, but it can also be used very, very effectively as an infusion.
So let's move on to buprenorphine. So this could be, we, we don't, it's hard to get data on a global, you know, like everywhere in the world get data on who's using what in, in what species, but buprenorphine is probably one of the most commonly used opioids in cats worldwide. And so we have multiple formulations of this drug.
So we have buprenorphine, the standard formulation, which is 0.3 milligrammes per mL, and that's the one that a lot of you are using IV or IIM, and I am putting up the dose here and a lot of us would expect that that would last between 4 to 6 hours, but of course we're doing our pain evaluation. So we do have different products that are licenced for use in, in cats in different countries.
We still don't have one in the United States, so we use the human equivalent. This, is that the same strength, like 0.3, 0.3 milligrammes in, in a meal, and we use that dose, but in the European countries and Australia and so on, you have the one that is labelled for use in cats.
And then a lot of you may have in the past or are still currently using the traditional buprenorphine and giving it transmucosally into the cat's mouth. So it goes into the cheek pouch or it goes under the tongue and it's absorbed transmucosally. Cause if it's swallowed, we know that opioids that are swallowed by cats really don't have much bioavailability.
They're all like passed through the liver and never make it to the peripheral circulation, but transmucosal is a good target. And so there is some data to show a couple of studies showing that given transmucozole, buprenorphine can be a nice way to continue out your analgesic. Plan and it's pretty noninvasive, you just drop it into the cat's, cheek pouch or under their tongue.
Now, it's not in every country that this product is available, but I am going to mention it because a lot of things are available in one country and then become available in another. So this is a concentrated solution of buprenorphine, so it's, you know, compared to the traditional one. This is 1.8 milligrammes in a mil.
And we give it at a very high dose, and actually, we do give it subcutaneously because of those two determinants, high concentration, high dose, and it does seem to last for 24 hours and its trade name is, is Symbidal. So it is labelled for 3 treatments, so you can give it, you know, once a day to cats, but we, we can't dispense it home. For owners to use because it is a controlled drug.
So in order to get our 3 days of treatment, we would have to have the cat return. So, you know, that's good and bad, but if they're in the clinic, they only need this once a day, not every, you know, 4 to 6 hours, like the traditional original buprenorphine. But if we want to continue opioid treatment at home, we need to be a little bit creative.
And so we have a problem, we think about it and some really clever people come up with solutions. And one is this transdermal buprenorphine solution that we now have in the United States and hopefully other people are going to start seeing it. So this is called Zorobium, and it's a transdermal solution of buprenorphine.
And you can see in the picture we're applying it just to the back of the cat's neck, and what we see is that it then continues to release these into the systemic circulation for up to 4 days. So we have a 100% compliance because we are putting it on, so we know when we send the cat home, it's on board, it's doing its thing. And user safety, obviously, when you apply it, you have to wait 30 minutes before anyone touches the cat until it's dry, but after that, the cat is safe, to touch.
And then just moving on to opioid-free analgesia, or OFA and a lot of you are thinking, well, look at all the benefits of opioids and what they can do, and we use them every day. So why would we want to try and not use them? Well, certainly, we've gone through opioid shortages.
We had a lot of opioid shortages. During COVID pandemic, due to manufacturing shipment, they were being, you know, required more for all the sick people and then remember we do have our our, our other veterinarians in some countries where they don't actually have access to opioids. So is opioid-free analgesia even a possibility?
So this is one of the first studies that came out, came out. They were looking at an opioid-free protocol in cats undergoing routine ovarian hysterectomy, and they looked at adults and they looked at kittens. And these animals were given, we call it often kitty magic, so it's a ketamine, dexedatomidine midazolam mixture, all mixed together, given IM and that's their anaesthetic protocol.
And these cats also got intrapertonealbupivacaine, and they also got meloxicam. And what did they find? Well, the results were, they were pain scoring them, and if they were painful, they were rescued with buprenorphine, which isn't in the actual protocol to start with.
And what they found was 25% of kittens needed to be rescued with this protocol, but 75% of adults needed to be rescued. So, certainly, we learned that it didn't look like this protocol, the the drugs in the anaesthetic, even though ketamine might have some analgesic effects, dexamedattonamine some, and the intrapertinal bipivicaine, meloxicam, it wasn't. It wasn't an opioid-free protocol, and they had to rescue.
So then there's this other study that was looking just at kittens and they gave the same, you know, similar IM injection that is their their actual anaesthetic, so they're completely unconscious with this triple mix or kitty magic. And then there was a control group that got nothing else, and then 15 out of 15 of those kittens needed to be rescued based on their pain scores. But if they also received meloxicam, and intrapertonealbupivacaine, only 1 out of 14 of the kittens needed to be rescued.
So there's a difference between, you know, the success in this study compared to the one I just presented, that kittens, it may be possible to go almost opioid free in some kittens. And the other thing that they showed, which was nice in this study was painful cats didn't want to eat. The ones that had good pain scores wanted to eat very quickly after their surgical procedure.
And this all goes down to individual variation. And this is why I'm gonna emphasise we need an outcome measure. So this is a film clip I took at a spay neuter clinic, and these are all the kittens in recovery after they've had their procedure.
So they've, they're all pretty hungry, they're eating away except this one cat. She's the outlier. Yeah, she's got if we looked at her, if we could look at her face, you can see she's got facial expressions of pain, she's hunched, she's painful, she's vocalising.
So there are some that fall through the cracks even when you choose good drugs. And she's a perfect example of nearly everyone else in that litter. They did great, but she did did not.
And so we do have to be aware of that. So, looking at, you know, what we were seeing in in kittens versus adults, long, you know, 2010 years ago, Doctor Paulson published this paper showing that when cats were less than 4 months of age and underwent ovarian hysterectomy, they had lower pain scores than adult or adult and pregnant cats. So it's not just about the drugs.
It's also about how much surgical trauma that we are creating. And if you look at this picture on the left, we're doing a paediatric spay here. And you can see the surgeon's making a very, very small incision, and here I took a quick picture in recovery, and you can see how small the incision is when we do the surgery when they're very young.
It's just big enough to get the spay hook in, so it's tiny, and the less trauma we cause with the surgery, the less inflammation, the less pain that we have. So let's just finish up with a couple of like how I would choose a drug for a specific case. So this is Lou.
He's one of my patients. He's, he's 19 years old and I needed to actually work on him. He needed to have an IV catheter placed.
I needed to get some blood work from him, get some radiographs, and do a fine needle aspirate. So he, he's an old man. He has quite a lot of issues.
He has chronic kidney disease. He's got osteoarthritis that we are treating. But for him, the perfect, opioid to do what I needed to do was butrophenol.
So just butterphennal on its own at 0.2 makes per kilo. He got lovely and sedate, he got all purry.
I was able to place his catheter, get his blood, take him to radiology, and get his fine needle aspirate on that. But then we have a very different case. This is Dora, a stray cat.
She was in a road traffic accident, and this is pretty dramatic. I mean, she really is broken. The students actually called her Dora because they said, this is Dora the Explorer, but she wishes she hadn't gone exploring from the little the cartoon movie, the kids watch.
So that was why, how she got her name, Dora. So you can see, this is pretty dramatic, but we were able to actually help Dora, and these are some beautiful orthopaedic work that was done at the clinic I worked at at the time, at the university clinic up in, in Michigan. And so you can see, but how, the question is, how did we get her through that and keep her comfortable.
So how did we manage Dora? Well, she came in on emergency, A very nice person found her at the side of the road, brought her in, physical examination, pain assessment, very, very high pain score, as you'd imagine. She was pretty dehydrated and in shock, really, so we stabilised her in the emergency room.
We placed a catheter, grabbed some blood work, but almost immediately we gave her intravenous methadone to see how she would respond, very, very quick, positive response. She was quite dehydrated, so we started her on IV fluids, and that's why we chose to hold off on her non-steroidals because of her dehydration at the time. She was pretty cold, low blood pressure.
We got her radiographs, which you've seen, pretty dramatic, and she was scheduled for surgery the following day. So what we did was when we took her to surgery, the anesthesiologists actually put her on methadone infusion. Overnight in the ER she'd been on intermittent boluses, but we switched that to an infusion and we used 0.1 meg per kilo per hour.
And then when she came out of surgery, we continued that for 24 hours. And then while she still had her IV catheter in, we went back to giving her intermittent boluses just to see how she, you know, if she was staying at a, with a very, very low pain score, and, and she was. Then we moved her to the recovery ward and her IV catheter came out, and then we switched her to buprenorphine.
Now, depending on where you are in the world, that could be transmucosal, buprenorphine. Once you see the video of her, I did not want to give her IM buprenorphine, multiple times cause she's very, very skinny and repeated IM injections can be painful. So we actually had the topical products, so we were able to give her the topical product.
So one application, 4 days, but not everybody has that. And then she, of course, could go back, could go on to her NSAIDs and we chose meloxicam. After surgery cause she was rehydrated, blood pressure was good.
So let's to finish up on a very happy note. Let's look at Dora, in her step-down unit in recovery, IV is out. And she's been transitioned to her buprenorphine and her non-steroidals.
So here she is. You can see she was probably a stray for a long time. We shaved her up.
She was a mess. But you can see her fracture repairs there, and she's walking pretty well. She's showing us very normal behaviours.
We, of course, we're pain scoring her carefully to make sure we're doing the right job. She's pretty chirpy. She's like, hello.
Hey Dora. Yeah, she really wants to get out of that cage. Dora.
So all very, very positive, but we used two different opioids in her. We started with a pure opioid, an agonist, which has that dual effect, at the NMDA receptor, number one choice for me in, in, in a dramatic case like this, but then after a few days, we were able to step her down. So I'm hoping that maybe makes all the different terminology and the different choices that you have a little bit clearer, like why we choose certain things.
So, thank you for listening in tonight and good luck with your pain management going forward with your kitty cats that are so special. Thank you.