Good evening everyone and welcome to tonight's webinar, an interactive session on acute pain management in dogs and cats. We're very excited to have Doctor Joe Morell with us tonight from the University of Bristol, on what proves to be a very exciting and interactive session. So please make sure you're paying attention and get ready to be involved.

A little bit of housekeeping before we begin, if you have any technical issues. There should be a little chat box on screen, and if you let myself or my colleague Anna know, we'll do everything we can to help out. If you have any questions for, for Doctor Joe Morell, if you hover over your screen as well, there should be a Q&A box.

If you submit any questions into there, whilst the talk is taking place, and then we'll have a short Q&A session at the end to try and get through as many as we can. So on to tonight's webinar, Joe graduated from Bristol University in 1994 and completed a clinical fellowship in anaesthesia at Bristol before undertaking a PhD also at Bristol, which she was awarded in 2001. In 2001, she moved to the University of Utrecht as head of small animal anaesthesia and was awarded her European Diploma in Veterinary anaesthesia and analgesia in 2002.

After a brief two-year period in New Zealand as a postdoctoral research fellow between 2005 to 2007, Joe returned to the University of Bristol as a senior lecturer in veterinary anaesthesia, where she divides her time between clinics, teaching and research. Joe's passionate about clinical pain management and pain research with the aim of promoting best practise in analgesia provision in patients. So without further ado, I shall hand over to Joe.

Great, thank you very much. Welcome everybody. I hope that you're going to find this webinar both enjoyable but also useful.

We've got lots of polling questions to test your knowledge about analgesia and hopefully advance your, your knowledge in this area. So what are we going to cover tonight? Well, I'm going to start off thinking about pain assessment because pain assessment is pivotal to good pain management.

I'm also going to include some information about the pathophysiology of pain. I'm then gonna move on and think about the pharmacology of opioids and NSAIDs, and then finish with the use of adjunctives such as ketamine, lidocaine, and dexamedotomidine and how they can be used usefully in clinical practise. So let's start off and think about pain assessments.

So the first polling question for you now. What's the most reliable indicator of acute pain in cats and dogs? Is it changes in blood pressure, changes in heart rate, changes in behaviour, or changes in respiratory rate?

Have you got the votes coming in? Yeah, we're up to about 70% of people, so we'll end that polling now. So, 4% of people saying changes in blood pressure, 29% changes in heart rate, 46% changes in behaviour, and 21% changes in respiratory rate.

So that's interesting, so there is some disparity between the answers. I would say that changes in behaviour are most reliable, because there's good evidence from a study that was conducted in a few years ago now, where, Oh, I can't advance my slides. Oh, that's it, which looks at the relationship between physiological factors and clinical pain in dogs using, a numerical rating scale, and what they found that there was that there was very poor correlation between.

Physiological parameters and pain. And I think that goes to show that behaviour is, is more reliable, albeit I think it's much more difficult to measure, and we have to be much more skilled at measuring changes in behaviour than we are, than we do to measure changes in physiological variables, for example. Pain is complex, it's a multi-dimensional phenomena, and it's important to assess both the sensory component of pain and the emotional component of pain when you're thinking about looking at pain in an individual animal.

The emotional component can encompasses things like pain, unpleasantness and distress caused by pain. And really we're thinking about the impacts of pain on the emotional wellbeing of that patient. So it's the, the distress and the, the nastiness associated with pain that I think encompasses the emotional component of pain in animals.

By contrast, the sensory component I think is easier to measure. It more comes down to where does it hurt and also how much does it hurt. So we're trying to quantify pain, quantify pain intensity and also look at the localization of pain.

So for example, this is a, a cat, and to look at the emotional component of pain, I think it's important to look at the animal from outside of the kennel and to see how it interacts with its environment. So this cat looks fairly relaxed. Looking at it from outside of the kennel and it sort of is interacting with me a little bit when I touch its face, so the cat doesn't look too depressed in this, in this video, but when we look at the cat's sensory components.

Then This is me trying to localise pain, so this cat's undergone a thoracotomy, and you can see that I'm pressing gently along the cat's thoracotomy wounds, and you can see that the cat is very resentful at the fact that I'm pressing along his wound. So if you think about the sensory component, I think this cat is showing definite signs of pain, which are more difficult to pick up when we were just looking at the emotional component, and that's why it's very important. That we assess both the sensory and the emotional component of pain in the individual animal.

The next polling question for you now, what is hyperalgesia? Is it when touch starts to elicit a pain sensation? Is it when a normally painful stimulus elicits more pain, or is it pain associated with an itch sensation?

OK, so about 80% of people have now voted. So if we end up polling. So we have 31% of people when touch starts to elicit a pain sensation, 66% of people when a normally painful stimulus elicits more pain, and a solitary person with pain associated with an itch sensation.

OK, so that's great, so most people got the correct answer. Hyperalgesia is when a normally painful stimulus elicits more pain than usual. Whereas allodynia is, is what we call when touch starts to elicit pain.

It's important to be able to recognise these phenomena because they're abnormal and they signal that we've had a regulation of the pain pathways or there's signs of central sensitization when the whole pain pathway becomes more primed to feel pain more acutely. And it's also important to recognise them because they indicate that more aggressive pain management is needed. So for example, this is a dog where I think is showing signs of hyperalgesia.

The, the dog has undergone a total hip replacement and the nurse is pressing quite hard along the wound. And you can see that when it gets to pressing around the face of the wound. You don't react.

And shows the pain sensation, so I think that's a good example of hyperalgesia. On the other hand, I think that this is a good example of allodynia, so this cat has undergone abdominal surgery. Mhm And you can see that I only have to stroke it.

And it shows a very pronounced . Response, pain response, indicating that the cat has allodynia. So both of these cases are animals that show signs of central sensitization, where we have to be more vigilant and more aggressive with our pain management.

So another polling question for you, when should you use a pain scoring tool to quantify pain in cats and dogs? In every case, it's important to detect and quantify pain. In what about in cases where you expect pain management to be more challenging, or thirdly, it's not really necessarily to formally quantify pain in cats and dogs.

OK, a majority of people have voted. 87% of people in every case, and, about 15% of people, in cases where it's expected to be challenging. So I think that's great.

Everybody recognises the importance of pain scoring. I think the in the ideal world, yes, in every case, we would detect and quantify pain, but I can recognise that that's quite difficult to achieve. And it depends very much on your nursing staff, I think, how, how many nursing staff you have and whether they can fit that into their daily schedule.

But more and more we're recognising that analgesic drugs have side effects, and so giving them according to their required need is preferable to giving them on a timely schedule. Therefore, trying to to detect pain and quantified pain in every patient is useful. So you use for pain scoring tool can make assessment of pain easier and it can only be used to guide the administration of analgesics.

It can be used to track changes in pain level over time and also to determine the need for rescue analgesia. So this is where you can say, well, if pain score reaches a fixed criteria, then please give more methadone, and you can write that up for a patient, give the nurses some autonomy in the administration of analgesic drugs, particularly overnight where they may not have backup of a vet on site at all time periods. A number of different tools are available now.

And we recognise that the best tools to use are the composite pain scoring tools, because these take into account both the sensory and the emotional component of pain. So the first tool that I'm gonna mention briefly is the Glasgow Composite Pain scale canine, because I'm sure most of you are aware of this scoring tool. It's the one that I would recommend that you use for dogs because it has undergone the most validation.

And it's freely available from the web. So if you don't have it in your practise at the moment and you want to search for it, put that into a search engine, and the site from which it can be downloaded will, will come up. It's developed by Glasgow Vet School and it's now available through a website called New Metrica.

It's a composite pain scale, so as I said, it takes into account both the sensory and emotional component of pain. It's validated, simple to use, it only takes about 5 minutes to complete, so it doesn't get in, you know, it doesn't disrupt your daily routine too much. It's also robust in a multi-user setting, so that means if different people are assessing pain in the same animal, they generally come up with similar scores.

So that's great if you've got a handover of staff, during the day. And also importantly, they, there's a defined intervention level for rescue analgesia. The score, total score with the Glasgow composite pain scale is either out of 20 if the dog is non-ambulatory or out of 24 if the dog's ambulatory.

So the criteria for rescue analgesia is adjusted accordingly, so either 5 out of 20 or 6 out of 24. What I suggest you do is that you laminate the scale and then use it to carry out assessments on dogs every 2 to 4 hours, depending on how challenging the patient is to analges. And then you can just write the pain score down in the animal's notes and you don't build up accumulation of paper throughout the day.

It's really useful to confirm that the response to analgesic intervention has been successful. And certainly what I find is that when you've used the scoring tool and you've been through the scoring tool, at the end of the assessment, you will come to some sort of conclusion about whether you think the animal is painful or not. Regardless of what the what the score is, so, even if you're not very confident in using the scoring tool, you will, you will come to some sort of useful assessment about whether the animal needs more analgesia or not.

It does have limitations. I think the main limitation is that it doesn't differentiate very well between animals that are very sedated and animals that are in pain. And you need to use a sense checker to differentiate between the two, because some of the questions asked about the animal's demeanour and how dull and depressed it is, and they can be dull and depressed because they're very sedated or dull and depressed because they're very painful.

Another limitation is that the effect of anxiety on the composite pain scoring tool is unknown. And it's possible that anxiety may trigger higher scores. Again, you need to take that into account when you're using the scoring system and use a sort of a sense checker about whether you think the animal needs more analgesia or not.

And I think it's not very robust to some types of pain, particularly ophthalmological pain, for example, where you can't palpate around a wound very easily. And it was certainly most widely used for post-surgical pain. For cats, we also have a tool developed by the Glasgow University Group.

Again, it can be freely downloaded from the web. It's quite simple, it comprises 7 questions. And again, they've set a criteria for rescue analgesia, and that's a score of 5 or greater out of 20.

And again, it has some advantages and disadvantages. It's fairly quick to complete and simple to use, which is, which is great in a busy practise setting. Also, if you're used to using the pain scoring tool in dogs, then it has a very similar look and feel to the dog scoring system.

So it's not a big transition to go over to the cat scoring system. Again, it's a composite scoring tool so it takes into account both the sensory and emotional component of pain. And it's validated with a defined criteria for administration of rescue analgesia.

Where it probably doesn't function very well, or I don't find it very useful is for cats that are fear aggressive or feral cats, where you can't interact with the animal. And I think that we're lacking a good scoring tool in this population of animals. Just to finish this section, I want to briefly mention two key principles of pain management, and they are preventive analgesia and multimodal analgesia.

So preventive analgesia is really the next step on from preemptive analgesia. So Really preventive analgesia is about giving analgesics early to prevent regulation of the pain pathways, but it's also about giving analgesics for long enough to prevent later stimulation of the pain pathways, so it's about timing and duration. And we know that preventive analgesia, certainly strategies that use preventive analgesia techniques in humans, have been shown to reduce wind up of the pain pathways and lead to more effective pain management overall, particularly in the acute post-operative setting.

What about multimode an analgesia then? Well, what is multi-mode analgesia? Is it using different drugs of the same class in combination, such as methadone and fentanyl?

Or is it using drugs from different classes in combination, such as methadone and meloxicam, or is it using different analgesia techniques in combination, such as the CRI of lidocaine and epidural bupivocaine? OK, most of the votes have come through now. So we have one person with the top option, 68% from different classes in combination.

And 30% using different an GCA techniques. So multimodal analgesia is using drugs from different classes in combination because then you maximise targeting different sites in the pain pathway and therefore you can provide more effective analgesia. If you use different drugs of the same class in combination, you're not attacking different sites in the pain pathway and therefore you don't have the same degree of efficacy.

I guess using different analgesia techniques is a form of multimodal analgesia if you're using different drugs. So if I said a CRI of lidocaine and epidural morphine, that would have been an example of multimodal analgesia. So moving on then, let's think about opioids, particularly about opioid pharmacology.

So opioids have lots of beneficial effects. They provide analgesia, and they also provide sedation, which may be advantageous but can be disadvantageous, particularly in the postoperative period when you want the animal to mobilise again and be up and about and eating and drinking. Which of the following would you say is a clinically significant side effect of opioids?

Is it 1, decreased blood pressure, 2, respiratory depression, 3, increased heart rate, 4, vomiting, or 5, increased respiratory rate? Majority of the results are in and the majority of people going through respiratory depression. Like I said that's an interesting answer because respiratory depression is very common in people given opioids, but certainly in a in awake animals given opioids, respiratory depression is very uncommon.

I think it's, you certainly see respiratory depression when you give anaesthetized animals opioids, but if you've got a conscious patient, you don't really need to worry about respiratory depression. I would have said that the most clinically significant effect of opioids is, is nausea and vomiting, particularly in awake animals, and there's a study that's just been published recently where they compared . Side effects with opioids, where opioids were either given according to pain score, or were given every 4 hours after a surgical procedure.

The dogs that were given Opioids, according to pain score, received much less opioids, and the incidence of vomiting in that group was also strikingly less than the incidence of vomiting in the dogs that received opioids every 4 hours. So I think that the vomiting is, is the most common or most important significant side effects of opioids. So let's go through some of the different opioids in their clinical pharmacology.

So if we start with Borphenol. Borphennil's a a kappa opioid receptor agonist. So because it's acting at the kappa receptors, analgesia is really of limited efficacy.

It's also very short acting, so if you do use it to provide analgesia, then you need to top it up very frequently, which makes it very unhandy for most surgical procedures where you're looking for a longer duration of analgesia either intraoperatively or into the post-operative period. But one advantage of buterfenil is it does have good sedative effects, so it's very useful for premedication of patients that aren't undergoing painful procedures such as imaging in non-painful patients. So for example, patients going for MRI.

Moving on then, we've got buprenorphine, so buprenorphine is a partial new receptor agonist. Which means that it binds well to the new opioid receptor, but it doesn't produce a maximal analgesic effect to that new opioid receptor. So it provides less analgesia than full new receptor agonists such as methadone or morphine.

One advantage of buprenorphine is it has a relatively long duration of action of up to 6 hours and it's the longest acting opioid drug that that we have. Gives you moderate analgesia, particularly if you're using a multimodal technique, then analgesia buprenorphine can be perfectly adequate. Another advantage is that you can give it by the oral trans mucosal route in cats, but I advise you not to use the multi-dose preparation by the oral transmucosal route because the preservative.

In the multi-dose preparation tastes really bad and cats really hate it when you give them the multi-dose preparation by the OTM route. There's also evidence to suggest that it's not very effective by the subcutaneous root in cats, and that may well extend to dogs. So if you're going to use buprenorphine, I would advise that you use it IM or IV.

The reason why we think it's not very affected by the subcutaneous route is probably because you need a high concentration in the plasma to drive it into the central nervous system where it can bind to the new opioid receptors and provide analgesia. If you give it subcutaneously, it only trickles into the plasma very slowly, so you never set up a good diffusion gradient for it to get into the CNS where it takes an effect. Pethidine is a full new receptor agonist, so we're getting on to our, more potent analgesic drugs now.

So it gives us good analgesia, but another disadvantage of pethedine is that it only lasts for about 60 to 90 minutes. So similarly to butterphenol, frequent top-ups are required. It also can't be given IV due to histamine release.

And because of the concentration of pethidine and the dosages that you need to give, so 3 to 4 to 5 mg per kg. It means that you need to give relatively large volumes, and that becomes painful when you're giving it repeatedly intramuscular, and that's another disadvantage of pethidine. So we've really gone away from using pethidine in our clinic at Bristol.

Moving on to methadone then obviously methadone's licenced, which is, which is a big advantage. It's a full new receptor agonist, so it gives us good analgesia. But another unique feature of methadone is it.

It's an NMDA receptor antagonist, and the NMDA receptor is important in central sensitization, so activation of the NMDA receptor drives central sensitization and up regulation of the pain pathways. So if you've got a drug that's an antagonist at the NMDA receptor, not only is it giving you a multimodal mechanism of action as an opioid, but also maybe more effective at preventing central sensitization. Although that's not really been borne out by clinical studies.

Has a medium duration of action of 3 to 4 hours. You can give it by a variety of routes, so IV, IM. We don't know about the efficacy of methadone subcuts.

It could be that the poor efficacy of buprenorphine subcuts also translates to methadone. So I would advise you to give methadone IV or IM and avoid the subcutaneous roots if possible. There's some evidence to support the oral trans mucosal.

Eating cats, and because methadone comes as a preservative containing preparation, cats don't like that preservative, so it's not a great drug to deliver by the OTM route. You can give it epidally, but I'd advise you not to use the preservative containing preparation epidurally because of concerns about the effects of the preservatives on the central nervous system. So we do give methadone epidally, but we use a preservative free preparation, but it only lasts for about approximately 8 hours, so shorter than, than, than morphine.

And I know people are using methadone by continuous rate infusion, but we don't really have any data to support use by CRI. And my clinical impression is that it tends to accumulate more than, for example, fentanyl or morphine when it's given by CRI. So there may be better drugs to give by CRI, when you want continuous analgesia.

What about fentanyl then? Well, fentanyl is a form you agonist, so it gives us good analgesia. And we've got two different forms available for administration, parenteral fentanyl, which is licenced in dogs, and there's lots of data to support its use in cats.

And then also we've got transdermal fentanyl patches. So parenteral fentanyl is licenced in dogs. It's only really suitable for administration intravenously because it's very short acting, so it only gives you about 10 to 20 minutes of analgesia after a single bolus.

But it's very amenable to administration by continuous rate infusion. So if you want to give it an opioid by CRI, I'd advise you to use fentanyl. But you do need to have some caution when using it in anaesthetized patients because you can see respiratory depression and effects on heart rate.

So I think if you're going to use fentanyl in anaesthetized patients, you should have Cainometry monitoring available to you so that you can detect respiratory depression promptly and instigate positive pressure ventilation if needed. And again you can have effects on heart rate, so you need to monitor heart rate and blood pressure so that you know whether you need to intervene. So opioids generally cause a reduction in heart rate.

So how would you manage a low heart rate induced by fentanyl in an anaesthetized patient? Would you 1 administer adrenaline, 2, administer atropine or glycopylate. 3, turn down the inhalant agent concentration, or 4 administer an opioid antagonist such as naloxone.

OK, majority of people have voted now and there's a bit of a split on this one. OK, so that's great. Nobody's gonna administer adrenaline, which I think is a is a good move, that's likely to induce arrhythmias if you give it, if you give adrenaline in a non CPR situation.

I think. I guess turning down the inhalant agent concentration is not such a bad thing to do, but it's not gonna directly manage the low heart rate caused by the fentanyl. So the most appropriate course of action would be to administer atropine or glycopyrolate, which is an anticholinergic, because opioids cause a reduction in heart rate by stimulating the vagal system.

So giving an anticholinergic is very effective at managing that. You could of course administer naloxone, an opioid antagonist, but then you're gonna leave the animal exposed to antinoisception during surgery or pain postoperatively, because that naloxone is also gonna reverse any endogenous opioids that the animal has circulating in its system. So it's not an ideal, ideal solution.

So, generally, if I'm using fentanyl by CRI and heart rate's dropping, what I do is I look at blood pressure. So, I try and measure blood pressure non-invasively, and if blood pressure's fine, so your mean is above 60, then I'm not too worried about intervening and giving anything to try and increase heart rate. But if blood pressure is falling below 60 mean and heart rate's also low, that's when I would step in and administer atropine or glycopyrolate to shift.

Heart rate back into a normally expected level for that patient. So the sort of dose that you would think about giving is for atropine would be 10 mcg per kilogramme IV. You need to wait 2 to 3 minutes after administering it before you see an effect, and it's important not to step in and just give more atropine too quickly because then you're likely to get into a situation where you have a tachycardia.

So give the atropine and wait for it to take effect, and it's usually very effective at generally increasing heart rate back into the normal expected range. Finally, I'm gonna talk about transdermal fentanyl patches. So these are still quite widely used in clinics, even though they're unlicensed in dogs and cats.

So it's a transdermal way of giving the fentanyl. But I think there are some serious considerations that we need to think about, with respect to the owner and concerns about abuse potential and disposal, because even when you take a patch off a dog or a cat, it's been shown that quite a significant amount of fentanyl remains in the patch, and that's obviously provides potential for abuse by the owner should they be the sort of owner that's going to abuse opioids. They're long acting, which is an advantage, but bear in mind that you have a 12 to 24 hour time delay before you start to see any analgesia because it takes that long before you get reasonable plasma concentrations of the drug.

Effects on respiration and heart rates are uncommon, probably because the plasma concentrations are relatively low compared to IV administration of fentanyl. But the big problem that I have with them is is that there's a real lack of clinical data to support efficacy. There's quite a lot of data showing evidence of pharmacokinetics and uptake of fentanyl into the system, but there's not a lot of data to show that they actually work.

So I think that if you have the capability to give drugs like fentanyl and methadone postoperatively intravenously, then you can much better go down that route rather than using the transdermal fentanyl patches. So moving on then, let's think about NSAIDs. So how do NSAIDs exert their analgesic effect?

Do they block the production of prostaglandins via COX enzyme inhibition, or, or do they block the production of aracadonic acid via phospholippase A2 inhibition? Do they have an effect on dorsal horn neurons via potassium channels, or do they activate descending inhibitory pathways from the brain? OK, most people have voted, much less of a split this time.

That's great. So, most of you got the right answer, which is brilliant. So they block the production of prostag glandins via the COX enzyme.

It's steroids that act one level higher up and block the production of our acadonic acid via phospholippase A2, so that's the difference between the action of non-steroidals and the action of steroids. NSAIDs are great analgesics, but there's no doubt about it, they have side effects, and that's what people are concerned about when they're using them. So one concern that we have is the effect of NSAIDs on the kidney.

So what do NSAIDs do to the kidney? Do they reduce renal perfusion in non-intensive animals? Do they cause direct nephrotoxicity?

Or do they reduce renal perfusion in hypertensive animals, or do they increase renal perfusion? Just let that run for a few more seconds. OK, majority of people are in now.

A bit of a split again on this question. Yeah, so I think there is some confusion about the effect of non-steroidals on the kidney. The correct answer is that they reduced renal perfusion in hypertensive animals, so prostaglandins are important to maintain renal blood flow during periods of of low perfusion.

So if you've got a normal intensive animal, then they shouldn't affect renal perfusion, but what we worry about is giving nonsteroidals around the time of anaesthesia because hypertension is so common during anaesthesia. So due to the renal effects, timing is really important around the time of anaesthesia, and certainly there's a lot of debate about when is the best time to give non-steroidals. So I'm gonna pose a question to you then, when should you routinely administer NSAIDs to the anaesthetized patient?

Is it before the start of surgery? I think once you check blood pressure's OK during anaesthesia, or should you wait until the animal's fully recovered from anaesthesia, or does it really depend very much on the patient? And their individual needs.

OK, most people here seem to be going forward depending on the patient. Yeah, I think that's what, I think that would be my pragmatic response. I think if you've got a, a healthy patient that is .

Norm intensive and you expect it to be normal intensive during surgery, giving them before the start of surgery is fine. Another approach is to is to give them once you've checked, blood pressure's OK during anaesthesia, but I would say that you never really know what's gonna happen with blood pressure, particularly during a long op. Another approach is to give them once the animal's fully recovered from anaesthesia and take a precautionary approach.

And I think in some patients that's the most appropriate thing to do. So I think it very much depends on the patients. So I take the approach that I administer them preoperatively and measure blood pressure intraoperatively so that I can manage blood pressure and maintain it at a normal intensive level unless the animal has preexisting renal disease, or unless I expect cardiovascular instability during anaesthesia.

So unless I expect significant blood loss, cardiac arrhythmias. Also it can be more difficult to maintain blood pressure when you've got a prolonged duration of anaesthesia, so if I think anesthesia's gonna go on for a long time, I'll delay administration until the animal's fully recovered. And also if I've got a very small patient that's going to get cold, I'll often delay administration because when they become hypothermic, it's more difficult to maintain their blood pressure within a normal range.

Another question then, different nsays are of equal analgesic efficacy, is that true or false? OK, most people in, majority of people going with false. Well, I think, I think for acute pain, I disagree with that.

I would say that most NSAIDs are of equal analgesic efficacy and certainly there's no real evidence in the literature that there's a difference between the efficacy of analgesics and non-steroidal analgesics for acute pain. I think when you're looking in the chronic pain situation and using them for osteoarthritis management, it does seem to be that in in dogs, certainly, some dogs will do better on one non-steroidal than another, suggesting that one non-steroidal is more efficacious in a patient than another one is. But we don't have that evidence for acute pain, so I think you should think about them as being of the equal analgesic efficacy.

The second question then is, again, a true false question is different NSAIDs are equal in terms of their safety, of side effects. Is that true or false? OK, we'll end that polling.

A lot of people are going for false on this one, vast majority. Well, again, I think, I think in individual animals, some animals seem to develop side effects with one non-steroidal and they wait with with another, but that doesn't seem to be a class effect, or, or you can't say that . One NSAID is consistently safer than another NSAID across a group of animals.

I think it's very much an individual effect. And we did look at VMD data to see about the relative frequencies of reported adverse events associated with NSAID administration in dogs and cats in the in the UK. And interestingly, what we found was that you were more likely to have adverse events reported with the newer NSAIDs, so drugs such as the COX2 specific inhibitors were more likely to be associated with side.

Now, I don't think that's because COX-2 inhibitors are less safe than the COX 2 preferential drugs. I think what we're seeing is an effect that we're more likely to report adverse events with newer drugs and therefore, And also there's been an increase in adverse event reporting over time, so the newer drugs are overrepresented. But certainly it didn't show any consistent differences between individual drugs and their safety.

So I don't think at the moment we have a lot of evidence to say that the, the non-steroidals that are licenced in dogs and cats differ significantly in terms of their relative safety. Moving on then, I want to finish with thinking about the adjunctive analgesic agents. And I'm gonna start off thinking about ketamine.

So, what is the major mechanism of action of ketamine? Does it block sodium channels? Does it inhibit the Cox enzyme?

Is it an MDA receptor antagonist, or does it block potassium channels? OK, we'll bring that poll to a close. The majority of people going with an NMDA receptor antagonist.

That's great, so that's the correct answer. So it's an NMDA receptor antagonist. So similar to how I was describing the methadone, the NMDA receptor is pivotal to central sensitization and up regulation of pain pathways.

So ketamine may be effective at reducing central sensitization, which makes it a very useful analgesic drug to have in our analgesic repertoire. So when would you use the ketamine CRI in dogs and cats then? Would you use it when you expect to have central sensitization and a chronic pain state?

What about you less discriminatory, you're gonna use in every patient as it decreases Mack of your inhalant agents. In patients with somatic pain or when pain is poorly controlled with an opioid CRI. We have a bit of a split here between options 1 and 4.

So yeah, I think, I think both of those. Options are reasonable answers, so I think certainly I don't think there's much value in using ketamine for a bitch spray or a va hysterectomy and a cat, for example, where you don't have up regulation of the pain pathways. So I think you need to have that in the back of your mind in terms of have we got the central sensitization and a chronic pain state going on.

But I also tend to use ketamine as an adjunct to good opioid analgesia, particularly if I'm using an opioid infusion and I think that pain is is poorly controlled. That's the time that I think about adding in ketamine into my analgesic repertoire. And certainly there is some evidence to support the use of ketamine to provide antiatoception during anaesthesia and surgery.

But the evidence isn't overwhelming and because we have best evidence for opioids to provide analgesia, I tend to use ketamine as an adjunct to a background of an opioid CRI such as fentanyl. The sort of dosages that that I use and dosages that have been published are a 0.5 metre g loading dose sort of given over 1 to 2 minutes, and then a 10 mcg per kilogramme per minute infusion during anaesthesia, reducing that postoperatively down to sort of 5 or 2 mcg per kilogramme per minute into the postoperative period, if you think the animal needs continued ketamine postoperatively.

So finally, what's the major side effects of a ketamine CRI? Is it reduced heart rate during anaesthesia or reduced blood pressure during anaesthesia? Or is it altered behaviour during recovery, or is it a tachycardia and increased heart rate during anaesthesia?

OK, we have approximately 70% of people going with altered behaviour during recovery. Yeah, I think that that's what I think the most important side effect of ketamine is. It's pretty good at supporting blood pressure and heart rate during anaesthesia because it stimulates the sympathetic nervous system, but altered behaviour during a recovery can be really problematic.

And I guess that's why I don't use it more routinely during surgery, because I don't want animals to be spacey during recovery. Unless I think that they really need that, that analgesia on board, and then it's a side effect that I'm more willing to tolerate. So moving on then to think about lidocaine.

So lidocaine may be an a useful adjunctive analgesic in patients with moderate to severe pain. In human in medicine, there's best evidence for using it in, in patients that have painful abdominal surgeries. That's where it's been shown to provide the most benefit.

But unfortunately there's very limited evidence to support use in dogs. Another question for you then, lidocaine CRI should not be used in cats for analgesia, is that true or false? OK, we'll just let that run for a few more seconds.

And we have about an 8515 split in favour of true. Yeah, I think that's, that's the answer that I would go for. Certainly there's evidence, that cats don't do very well hemodynamically when they're administered lidocaine during isofluorine anaesthesia.

We haven't really got the data in awake patients to say what happens in the awake animal, but certainly during anaesthesia, then the benefits that you get. Hemodynamically in terms of the, the max bearing effects of isofluorane aren't outweighed or or outweighed by the negative hemodynamic effects of lidocaine. So lidocaine CRIs are not my first choice for analgesics in, in cats, and I very rarely use them.

If I'm gonna use lidocaine in dogs, I go for the sort of published dosages, which is a 1 milligramme per kilogramme loading dose, but I tend to give that slowly over sort of 5 to 10 minutes intravenously. And then a 50 mcg per kilogramme per minute CRI. It's important to remember that lidocaine is very sedative when you give it intravenously.

And so it has a significant max bearing effect for the inhalant agent, so you need to monitor anaesthetic depth carefully and turn down the concentration of your inhalant agent accordingly. And finally then, I want to think about Dexedatomidine or meatomidine, because this is a sedative agent, but it does have useful analgesic effects. But because the analgesia is very short-lived, we need to give the drug by CRI when we're using it for for analgesia in the post-operative period or intraoperatively.

Again, it also has a significant max bearing effect for the inhalant agent, so if you're using it intraoperatively, you need to monitor depth of anaesthesia carefully and turn down your concentration of inhalant agent to an appropriate level so that the animal's not too deep during anaesthesia. Obviously when you're using dexammeatomidine or metoomidine, you need to bear in mind the cardiovascular effects of the drug. So it, I wouldn't use it in patients with significant cardiovascular disease or in dogs with mitral valve disease, where slowing the heart rate will increase the regurgitant fraction and therefore reduce cardiac output.

It tends to have a variable effect on blood pressure depending on the dose. So if you give very low doses by CRI, you may see predominant hypotension due to sympathylysis, where the lower sympathetic nervous system tone leads to a lower blood pressure. If you use slightly higher dosages, that will tend to support blood pressure due to vasoconstriction, but it will also be associated with a large drop in cardiac output.

So just because your blood pressure's higher doesn't necessarily mean that your circulation is well supported. And so, and as with the other adjuncts, I think it's best used as an adjunct to opioid analgesia. So if I'm gonna use a DEX CRI, I'll pre-med with dexamed attoidine at sort of 1 to 3 mcg per kilogramme IV and then give the CRI at 1 mcg per kilogramme per hour.

And at that sort of dose, you shouldn't see hypotension, but you're not gonna see a big hypertension either due to vaso constriction. So it sort of tends to be relatively cardiovascular stable, at least in healthy patients. One thing we do need to think about with Dex melatoninine given by CRI is urine production.

So what does Dex melatoninine do to urine production? Does it do nothing? Urine production's unchanged.

Does it increase urine production, or does it decrease urine production? Just let that run for the last few seconds. And we have approximately 2/3 of people going for a decrease in urine production.

Yeah, that's, that's not the right answer. So the right answer is it increases urine production because it decreases ADH production. So that's important clinically, because if you've got an animal on a Dex CRI, you need to be aware of this and empty their bladder if they're not capable of voiding bladder, voiding their bladder spontaneously, for example, in an animal that's, that's anaesthetized.

Or postoperatively, if you're using a DEX CRI, make sure that you take dogs outside the toilet frequently so that They can urinate spontaneously. And that's one advantage of a Dex CRI when you use these sort of low dosages, is that you tend to get arousable sedation, so the dogs can be taken outside and will walk, but when you leave them undisturbed in their kennel, they'll be relatively sedated and also getting analgesia at the same time. It is important to monitor heart rate during a DEX CRI because heart rates can be quite low.

So again, it's a question of monitoring blood pressure. And if your blood pressure and your heart rate are low, then you've got one option would be to stop the CRI if you're very concerned. Or the other thing to do is to think about atropine, just to shift heart rate back into a normal dexedatomidine range.

So you're not talking about shifting it in a dog back up to 100 or 120. You're thinking about shifting heart rate up to about 50 to 60 beats per minute, where blood pressure will be that little bit higher. But I think if you're gonna use a Dex CRI it's important to both monitor heart rate and blood pressure to confirm that they're within the normal range.

So finally then, we've got a choice of adjunctives. The question is, is which one do I choose? Well, I think there's most evidence to support the use of ketamine as an analgesic adjunct, so that's the one that I'll tend to go for next after my opioid CRI.

I also tend to add in adjuncts sequentially so that I can start and stop them independently. I don't mix them all up in the same. Dripp back and give them by the same infusion rate because you have very little autonomy over starting and stopping them independently.

But if you do use them in combination, you may need, may be able to adjust the doses down from the doses that I've I've given you because they'll have synergistic effects with each other. But if you're gonna use adjunctives, it is important to have a solid opioid base before adding them in, because I don't think there's enough evidence really to start using them on their own. So in conclusion, I think pain assessment is absolutely fundamental to good pain management, and so using one of the Glasgow tools either for cats or dogs, is, is pivotal to to getting analgesia right.

We want to be using multimodal techniques for improved analgesia, so opioids and endstays form the mainstay of analgesic regimens, but adjunctives can be useful, particularly in patients that are very difficult to analges. And I'd be very happy to take any questions. Wonderful, thank you very much, Joe.

Very good webinar there, very interesting, and I hope everyone enjoyed the interaction. As Joe mentioned, she's happy to stay for a little bit to answer some questions. Had a couple come in already, so we'll get started straight away.

So Richard Bennett asked, what about Dipperone or is it not available in the UK? It's not available in the UK, because it causes, has effects on white blood cells and so it's not, it's not legally available in, in the UK. There is quite a lot of evidence to suggest that it's a good analgesic if it was available.

OK, thank you. Jill said great webinar, always good to get good feedback. We've got a question.

What about burophenol as the CRI? Butorfenol is a CRI. Yes, yes, I don't have much experience with it as a CRI, .

I know people that do use it dosages are sort of 0.1 mg per kg per hour, but I think you can better use, if you've got it available to you, you can better use fentanyl as a CRI because you'll get better analgesia from fentanyl than you will do from born, even if you're giving buorphennil continuously because Borphennil is a kappa agonist rather than a full new agonist. Thank you very much.

Cameron said great webinar, thank you. What sort of bioavailability is offered for dogs with oral methadone? The oral opioids are not very bio bio bioavailable in dogs and cats because there's a very high first pass metabolism effect in the liver.

So they're not really drugs that are useful to give orally. Mm. OK, Sue said thank you, very, very helpful, which obviously very good.

Sally's asking, is the level of analgesia of medicinidine different in the dog or cat? Or different to dogs and cats. .

We don't I mean, there are studies that show them to be analgesic in both dogs and cats. My feeling is, is that you get equipotent analgesia in dogs and cats. I don't think that they work particularly better in one species over over another, and we use them quite commonly in both dogs and cats, particularly for neurotype surgeries, where we want a very stable, patient hemodynamically, and obviously we want them to be very stable in terms of their plane of anaesthesia.

Mm. OK, I have another question here. Is there a difference between cats and dogs with regards to renal perfusion under GA when considering perioperative NSAIDS?

We don't have any data to, to tell, to tell us that, . In, in normal cats, and in normal dogs, GFR is well maintained, even when you give a nonsteroidal. It's only when you have, hypertensive states that GFR will tend to, will tend to fall.

But I'm not aware of any data that's compared relative effects in dogs dogs and cats. OK, thank you. Just have a quick question here about, blood pressure.

So for nurses who are monitoring, I think you mentioned 60 is a low blood pressure, so when would you start to, to worry? 60s are cut off, so we'll start to be more aggressive in our management of blood pressure once, once the mean falls below 60. And so we take a stepwise approach.

So the first thing that I would try and do is turn down my inhalant agent, and if I can't do that with, with depth of anaesthesia as it is, then I would probably give a top up of methadone inoperatively at sort of 0.1 meg per kick to allow me to reduce my inhaling agent further because that'll give you a more balanced anaesthesia, analgesia technique. I'll then think about a fluid bolus of sort of, 5 to 10 mL per kilo in an animal that doesn't have, significant cardiac disease.

But in my hands, unless you've got overt blood loss, I don't find fluid bonuses to be very helpful. And then my third intervention would be to use ephedrine, which is a drug that you can. Get from MBS, it's not licenced in animals, it's licenced in people, and it's a sympathomimetic, so it will tend to increase heart rate, increase blood pressure.

Through some vaso constriction and an increase in myocardial contractility, and it's a drug that is, safe to use with non-invasive blood pressure monitoring, so it's very effective at increasing blood pressure if other if your other techniques haven't worked. OK, great, thank you, very helpful. What are your thoughts about NSAIs for postoperative pain relief in cats, post castration and spay?

I feel cats really shouldn't be treated differently to dogs and bitches who routinely get NSAIDs post-op. Yeah, I think, I mean, there is evidence that cats show behavioural changes after neutering for up to 3 days. So I think that giving 3 days to analgesia postoperatively to cats is, is warranted too.

Mhm. OK, great, thank you. I have a question here.

We have, we only have access to methadone as a full new agonist. Any tips on dose rates or how best, to use it to manage pain? So we use dosages generally 0.2, 0.3 mg per kg.

Although the licence dose is much higher than that, you're much more likely to see side effects when you use the higher dose range and you get good analgesia at 0.2 to 0.3 mg per kg.

And we will generally write animals up for postoperative analgesia every 4 hours with methadone. Maybe 0.2 migs per gig if you've got an NSAID on board, 0.3 migs per gig if you can't give them an NSAID for, for some reason.

And then we'll combine that with pain scoring and adjust the dose up or down depending on, how well they, they're born. Great. Thank you very much, Joe.

That appears to be all the questions, so we'll just give 11 last chance if anyone has any final questions that they want answered. After the webinar, for the attendees, you will have a box pop up that's just asking, for your feedback or feedback's very useful for us. I don't think there are any more questions coming in, so I say thank you very much, Joe, for a fantastic webinar.

I hope you all enjoyed the interactive session. I'll see you in another webinar soon. Good night.