Hello everyone and thank you very much for joining me on this webinar, anaesthetic drugs, premedication Pharmacology and Patient considerations. You may have heard the saying before, the safest anaesthesia is the one you know, but I always challenge that saying by saying, well, actually, if that is the case, know the one you're doing. Let's really understand the drugs that we are giving to our patients.
And interestingly, if we have Have a look back onto our SIPA study that we always refer to in veterinary anaesthesia. This is that confidential inquiry into perioperative small animals fatalities, looking at things that contributed to morbidity mortality. There actually wasn't a single drug.
That was responsible or found to be an increase in anaesthetic risk for our patients. So it's not necessarily the drug that can cause patients' problems, it's what happens when that drugs on board when we monitor them and do we take into account how that is going to affect our patients. So it's not necessarily drugs that get our patients into trouble, it's perhaps not fully understanding how that drug is going to work with that patient.
You may have also heard the same, there are no safe anaesthetic agents, and there are no safe anaesthetic procedures, there are only safe anaesthetists. And I think that really does echo the previous saying. We just really have to understand what we're giving our patients.
So in this webinar, we will have a look at what actually is anaesthesia, some common anaesthetic drugs, and we will have a look at the pharmacokinetics and dynamics of how these drugs actually work once they are in our patient's body. I think it's always great that we start off thinking about anaesthesia as a holistic process, which is, it's a Greek word ultimately, that's what anaesthesia is a Greek word for without sensation. And the important thing is with anaesthesia is that it's reversible.
Otherwise, if it wasn't reversible, we would have without sensation leading to euthanasia or death. So we've got 3 factors in our anaesthesia triad here. We've got muscle relaxation.
We want to be able to restrain and immobilise that patient so that we can handle them. We want to relax that skeletal muscle. We also want to provide analgesia from a complete welfare perspective, but also for the ongoing complications that can occur if our patient remains in pain.
And of course, we want to prevent this awareness and Response. So we do want our patients to be unconscious. So this is our anaesthesia triad.
We use a lot of different drugs to achieve this, but ultimately, anaesthesia means without sensation, without being aware of what's going on, and then without being able to have that sensation of pain. There are many stages of anaesthesia. There are, well, depends on what you read, but there could be 1 to 4 or 1 to 5.
I like the stages of anaesthesia, including 1 to 5 because this does include the pre-anesthetic assessment. And this is really important because it allows us to fully understand our patients' comorbidities and disease processes and health status so that we can plan. Our patients drugs accordingly.
So I like to include this pre-anesthetic assessment. This starts weeks before they come in for their procedure. This could be, they come into a consultation, we're doing a vaccination, we notice their teeth are really bad.
We know we're going to have to anaesthetize that patient for a scale and polish, possibly even extractions, but we, we also take a heart murmur. Oh, no, OK, let's investigate. That, or perhaps they're a bit older and we run some P3GA bloods.
OK, some kidney markers have flagged up. Let's stabilise that before we anaesthetize that patient. Let's consider how those will impact our drug choices throughout their patient's anaesthetic experience.
We didn't have pre-medication, we have the induction of anaesthesia, the maintenance of anaesthesia, and then, of course, the recovery of anaesthesia. And if we are focusing on pre-medication today, We actually will be using our pre-medication drugs throughout the rest of the induction, maintenance and recovery phase. These one-off doses that we potentially give our patients in the pre-medication phase, they might not last long enough all the way through the maintenance and into the recovery phase of our patients anaesthesia.
We've got to be planning that patient's anaesthetic drug choice and dose and repeated dosing again from pre-medication. All the way until they're in that recovery ward, waking up from their anaesthesia. So we use a lot of drugs throughout their patient's anaesthetic experience to achieve this, not just in pre-medication, but we will use a lot of drugs throughout their whole experience.
And I quite like comparing it to a cocktail. I compare it to the Long Island iced tea. Look at the volume of this drink.
There is quite a lot of volume in there. If we Just chose 12, maybe 3 drugs for this patient's anaesthetic, then we are going to have to use very big doses. We're going to have to fill that cup up, that glass up with quite a high concentration of drug.
And the effect of that is that our patients are going to hit the floor. It's like filling up this Long Island iced tea glass with just pure vodka or something. You are not going to have a wonderful time.
For you to have a wonderful time if we just use lots of little drugs throughout the patient's pre-medication induction maintenance phase, if we use lots of little doses of these drugs, so instead of the tequila, we've got aromazine. Instead of that vodka there, we've got metaamidine, and the white rum, we've got a benzodiazepine. If we can just use lots of little doses of drugs, what we actually achieve is a balanced anaesthesia.
We can work on lots of different pathways of the pain pathway. And also it allows us to reduce the drug doses of everything we give. So that's why our patients can enjoy this full glass of anaesthesia, because there's lots of little things in there.
They're not going to get such strong dose dependent side effects. So just breaking down the terminology of balanced anaesthesia, because we talk about balanced anaesthesia and we talk about multimodal analgesia. What is balanced anaesthesia?
Well, this is something we can do when we pre-medicate our patients, and this is once again giving lots of little drugs. So why? It allows us to reduce other drug doses, we can add a little of this and a little of that allows us to reduce the overall dose and hopefully dose dependent side effects that we give our patients.
And by using lots of other drugs as well, we can do something called MAC sparing, so minimum alveoli concentration sparing, that allows us to reduce our volatile agent. It will also allow us to have a very smooth induction process. It will allow us to decrease the induction doses and maintenance doses of the anaesthetic drugs we give, and also it will let us have our patient nice and smooth and completely anxiety-free, hopefully, into the recovery period.
So we can sedate and provide that anxiolysis, remove that pain, that fear. From the recovery period just by premedicating our patients with the concept of balanced anaesthesia. Of course, we do want to preemptively provide that analgesia.
We do want to be able to provide muscle relaxation for the surgery, but also just allow us to handle that patient and perhaps place an IV or restrain them for their induction of anaesthesia without that fear, without those catecholamine induced. Rushes of adrenaline that could really stress our patient out and predispose them to cardiac arrhythmias. Just focusing very quickly on the recovery period, what actually is the recovery period before we move on and start talking about pre-medication, the recovery period is phase 5 and the type of phases I like to have, I like to look at and this is actually when we have the start of our patients being able to recover from the anaesthetic experience.
So, The anaesthetic agent that has maintained their unconsciousness has been stopped. They are now allowed to return to their normal state again. That normal state being consciousness, not necessarily them running around the kennel room anymore.
But the thing is, we have to think about the recovery period all the way from the pre-medication phase, especially considering when we look at that step. The study that I referred to earlier on, we lose the majority of our patients in the recovery period for a multitude of reasons, but we have to think about the drugs we give our patients in the pre-medication phase, potentially affecting our patients all the way into the recovery period. And I have put here, I put the excited Labrador versus the overweight pug getting aromazine.
Now let's imagine your practise has a very routine protocol, and you've got very standard drugs that you use. You're instead you're tailoring those drugs to your convenience, the things you understand. OK, I'm more familiar if we use 0.02 mes per kg of aromasin, for example.
I'm familiar with that, but perhaps that's not what my patient needs. That's not very Focused and targeted to my patients. So let's think about that excited Labrador.
Perhaps we give that 0.02mg per kiromazine dose, and it works very, very nicely for them. Our Labrador calm down, we're able to handle them.
The tail becomes just a little bit less waggy, but they still walk into the anaesthesia induction area. But let's consider we use the exact same dose for our overweight pug. So we still use 0.02 for our overweight pug, so potentially Now they've got this slight overdose of the drug, because we've given it to their fat weight and not necessarily their ideal body weight.
And then we've given this drug that we know also relaxes the soft pharyngeal tissue. So when our plug goes to recover in the recovery phase of its anaesthesia, not only has it had more drugs than anticipated because it was overweight, it actually has quite a lot of soft, pharyngeal tissue that's all obstructing the airway now. So we've got to think about how our patients will recover.
Based on what drugs we gave them the pre-medication phase. If we have, say, a or a staffy, you know that those are the dogs that like to, to cry throughout their entire hospital experience whilst they're awake, and they make that shrilly noise. If they're doing that at the pre-medication phase, and then we pre-medicate them and they're still doing that, let's anticipate that those drugs potentially weren't enough to last them all the way through to a nice easy recovery as well.
If, if they're Shrilling their voices and they're being noisy and they can we pre-medicate them and then they're nice and quiet. Perhaps that is going to be enough for the recovery phase. But let's, let's just consider it.
I mean, there are a lot of things that will impact the patient's recovery period, and all the way down from just patient specifics and also what the anaesthesia was like, what agents do we use the procedure and the time, but let's consider how important premedication is to recover those patients. Now, in terms of anaesthetic drugs, we've got quite a lot available to us. We've got opioids, different sedatives, different kinds of induction drugs for anaesthesia, benzodiazepines, anticholinergics, local anaesthetics, and volatile agents, non-steroidals, so many types of anaesthesia drugs.
And although we are talking predominantly about pre-medication drugs today, these pre-medication drugs will have an effect on all of these other aspects on the bottom line for our patients anaesthesia. So we are going to cover them as well. Now we want to give opioids to our patients who are undergoing painful procedures.
We have got 3 different types of opioid receptors that we talk about. We have the new, the delta, and the kappa. The mu and the delta receptors are in the brain and the spinal cord.
The kappa receptor is primarily in the spinal cord, but we use these receptors to put analgesia out there before we introduce a painful nox to stimuli to our patients, just so that they don't respond as As profoundly. And one thing we do have to be mindful of is that opioids can also cause a bit of euphoria, potentially even dysphoria, and it can actually increase locomotive activity. So you can give just an opioid to your patient and they almost get a little bit frantic sometimes.
So we do like to add our sedation drugs in there. They have a very nice effects together when we use opioids and sedations. And, we will be able to handle our patients quite nicely.
So these are the typical new opioid drugs that we have available to us. And we're going to talk a little bit about the bunil though, because although there's some new action, it's not necessarily the one we want. But when we talk about opioid receptors, we talk about Agonists, full agonists, partial agonists, and then we talk about antagonists.
So agonists, I would like to think of it as a doing drug. It's doing something when it's on that receptor, and antagonists means it's kind of a stopping drug. It's potentially stopping something occurring when it's on that receptor.
We talk about full new and partial mute agonists. So those are opioid receptors that are going to be doing something for our patient. And the new receptor is the primary one we were anticipating quite painful procedures to have happen to our patient.
When we have a full new agonist, what that means is that we have this perfect fit of the drug molecule onto the drug receptor, and you can kind of see it like this lock and key effect here. Now, when we have a partial agonist. We still have the drug being able to lock onto the receptor, but it doesn't bind fully onto that receptor and unlock its full potentials, if you like.
So you can see that with the pink partial new agonist down here. It's able to bind onto that receptor, but we're still missing a key part there. So we are going to get some analgesia, but potentially just not a full amount of analgesia, maybe just a moderate amount of analgesia.
Let's break down the drugs that we have and what receptors they go on. We've got methadone, so this is our full new agonist drug, and it also has some NMDA receptor activity. So this is on the spinal cord.
Methadone is really good for moderate to severe pain because it can bind fully onto that receptor. Buprenorphine, this is a partial new opioid drug. It will partially bind onto that receptor, providing mild to moderate pain relief.
This means we don't really want to be going and doing a very painful procedure, perhaps a, a fracture repair or something like that with just buprenorphine on board. It's going to bind onto that receptor, but it's not going to be able exert its full effect. We then have fentanyl.
Fentanyl is a very, very short acting full full new receptor agonist, and this is wonderful for severe pain. So if something quite painful is popping up in our patient at that moment, maybe it's a fracture reduction in that moment. Maybe we're about to do some really painful.
Pulling on some ovaries, we can reach for fentanyl. It's going to work on that receptor. It's going to give quite a profound amount of pain relief and it doesn't last for long.
So it might be able to get us through that very painful period as a bolus or we can put them onto a CRI, but then that methadone will still be there in the background. We then also haveburophenol, and butterphennil does get a bit of a bad rap because it is a kappa agonist and a new antagonist. Now, we still do like our kappa receptors.
They do provide a lot of pain relief for visceral pain, so organ pain. And so it's quite good if we're doing things like endoscopy or maybe we're doing an ultrasound on our patient and we're going to be pushing quite a lot on their painful abdomen. But unfortunately, it's not really going to be helpful for any of that somatic pain, that cutting through muscles.
So that's why we don't really like it for our patients that are going to have a bit more of an invasive procedure. But there is still some pain relief. It is minimal, but it does get a bad rap that we shouldn't be using it.
I do think there absolutely is a place to have metorphinol on our shelves. We just have to consider what type of pain our patient will be experiencing. So we can kind of group all of these opioids and their side effects with quite common things that we might see.
We can see respiratory depression when we give opioids. We know that we just have to step in and potentially support our patient breathing under anaesthesia. It does also have a bit of a cough suppression activity as well.
That's why we do like the tool when we do bronchoscopies because it is going to be stopping that cough reflex from occurring. It can reduce the heart rate, and this is By increasing that vagus nerve tone, that vagal tone. It will reduce max, so that's our minimum alveolar concentration.
It means we need less of our volatile agent to keep our patient anaesthetized. It can reduce that lower esophageal sphincter tone, so potentially predispose our patient to a bit of reflux or regurge. It can induce Vomiting, and it can make them a bit nausea.
It can nausea, sorry, it can increase the incidence of vomiting, by going right to the vomiting centre in the brain. So let's just be careful how we use this drug, especially this might happen with hydromorphine or morphone, hydromorphone or morphine. Our patients might vomit preoperatively.
Before we start the patient's anaesthesia, before we've got control of the airway. Let's think about when that might be a problem. Perhaps if they've got, brachycephalic obstructive airway syndrome, and we don't want them to be vomiting and sedating at the same time, or perhaps I've got an esophageal foreign body.
We don't really want them vomiting. So let's be careful how we choose these drugs. Can we give them an antiemetic at the same time?
Can also cause pantene in dogs. This will reset the thermo centre in the brain. It doesn't matter how slowly you get this drug, whether it's over 5 or so minutes or you bolus it in.
If a patient is conscious, they typically will pant. And it's nothing to be like too worried about. They, it's very, very transient it will pass.
We can get a dose dependent Hyperthermia in cats when we use opioids, and sometimes we will get old cats receiving an opioids and they get this rebound hypothermia and they actually get quite a lot warmer. But to be honest, the cats don't really seem very affected by this. I think they kind of like being a little bit warmer and it's very transient, it will only last as long as that opioid is on board and that sometimes that temperature goes up to about 40 or so degrees, but you don't have to provide active cooling or antagonise the drugs or anything like that.
It can cause urinary retention through increasing levels of anti-diuretic hormones. So let's just be mindful if we give our patients opioids, let's express their bladders on that recovery period and let's just make sure they are nice and comfortable. It can cause the pupil to change, it can constrict or dilate depending on if it's a cat or a dog.
We're gonna get meiosis in the dog and drysis in the cat. And the wonderful thing about opioids is if there is an emergency, we can antagonise these drugs. These are all things to keep in mind.
Having a look at sedatives, we've got lots of different terminologies when we talk about sedatives. We can talk about drugs being anxiolytic with their doses, so that's just to reduce anxiety, provide that mental calming, decrease the patient's movement, make them less concerned about the environment that they're in. And then we can provide our sedatives to have full sedative action, so that's sleepiness, and they become less responsive to stimuli than if they were just having it at an anxiolytic dose.
Typically though, with a sedative, you can still rouse them. If we give too much sedatives, we can induce this period of nar. And, and especially partnered with an opioid as well.
This is just a, not necessarily what can happen when we give just plain sedatives. It's more if we give a very big dose of an opioid, we can provide this sedation through narcosis. But we do have these three main anaesthesia sedative drugs that we talk about and use quite a lot in everyday practise.
So we're going to break them down together. Acopromazine, this is a drug that will sedate, provide anxiolysis to our patients, calm them down and mood alter them. So this works at the dopamine receptors and the serotonin receptors.
So we've got two dopamine receptors, we've got D1, D2. They And have different functions of memory, attention, impulse control, and regulation of renal function. Think about when we use dopamine as a CRI under anaesthesia, and our D2 receptors are there for locomotion, attention, sleep, memory, learning.
So this is where that drug works. The thing is about aopramazine is the sedation is less reliable than alpha 2s. Sometimes you give a dose to your patient, and they're still running around wagging the tail as if you've never touched them with a drug.
And then you give aromazine to some of your patients and they go flat on the floor and you to get a trolley or a stretcher just to move them from the ward into the operating area. So the sedation is, is less reliable. The thing with aromazine is there is no analgesic properties in it.
So you might actually have a sedated patient that is experienced pain and perhaps in the post-operative period when you try to perform a pain score, is actually unable to respond appropriately to the painful stimulant you're introducing because they could still be so sedated. Another thing about Aopromazine is it does last a long time and you cannot antagonise this drug. Once it is in, it is in.
So if you have got a, let's think about that overweight pug that potentially has got that muscle relaxation all around that soft pharyngeal tissue, and it's potentially going to become, obstructive in the recovery period, we need someone sitting with that dog the whole time. We cannot antagonise that drug and get it out. Now when we administer this drug, depends on what you read, it can last, well, that, that onset of action can last anywhere between 10 to 40 minutes if we give that into the muscle, and then if we give it intravenously, it can be on board kind of within 5 to 15 minutes, to be honest, but it does.
It lasts for a long time, about 6 hours, but some of the big effects will start to wane away 3 to 4 hours, which is why it's great for recovery. Our patients will have it on board from their pre-med, they'll recover with it on board and then they'll still get up and walk out of the door when their owners come and pick them up. There is this hepatic metabolism involved in clearing this drug.
It is very highly protein bound. So let's be careful giving it to our patients that potentially have liver disease and less proteins available. They may get a subjective overdose.
It is lipophilic, so it will cross the blood-brain barrier and most importantly, the placenta. So let's be very careful if we're going to be using this drug in a patient that is undergoing a caesarean section because those little foetuses, they will be getting it as well. Looking at what this drug does to the patient's body, it doesn't necessarily on its own affect the respiratory rate or the heart rate of our patients.
However, it potentiates the other drugs that do that, i.e. Our opioids.
So we can start to see some perhaps profound reduction in respiratory rates. Under anaesthesia we need to step in and help that patient or drop that heart rate as well. Another thing about aopromazine, although we get those really nice sedative effects up in the brain, it can antagonise our alpha one receptors and in doing so, it can cause this vasodilation.
If we cause a vasodilation, it can cause a hypotension from that and and it can actually also cause a hypothermia as we lose a lot of heat out of our periphery, and it also resets the thermos centre in the brain. Other effects of Aceromazine, and this is very, very interesting because I've absolutely seen these first few points occur in my patients and not really thought anything about it until after the drug has been given. So aromazine does have some anti-arrhythmic effects.
So for example, there was a patient. Of mine that was, had an arrhythmia. We put on a conscious ECG and we found that there was some DPCs occurring in there, and we thought, right, this patient just has to go off to cardiology and be assessed.
But this patient became a little bit stressed and a little bit unhandable in the hospital, so we gave it its pre-med. And then once we've given it its pre-medication basedromazine, it then went off to cardio and we couldn't pick up on that arrhythmia anymore. I was like, damn it, we, you know, the ECG is normal now, we can't pick up on that arrhythmia anymore.
So just be mindful of that. It can be a good and a bad thing, a good thing if you potentially have a rhythmic res, but also a bad thing if you're trying to investigate the specific arrhythmia. It does have antihistaminic effects as well.
So we would not want to be using this drug if we Doing dermal skin testing in our patients. If we're anaesthetizing our patients, sending them off to the dermatology department so that we can do dermal skin testing and find out what our patients are allergic to. We do not want to pre-medicate them with aromazine.
They will not react in the way that we hope that they will, or won't with their dermal skin testing. We can see this decrease in impacts cell volume due to splenic dilation, literally within 30 minutes of getting this drug, the spleen. Accommodate so many of these red blood cells and they all rush into the red blood cells.
We, they saw the red blood cells all rush into the spleen. So I don't really want to be using this drug if we're going to be taking the spleen out. Now, does this then affect the coagulation status of our patients and platelet aggregation?
It's not really reported in any type of morbidity mortality rounds that we can Have aromazine exacerbating a coagulopathy. However, we potentially don't really want to be using aromazine in our patients that are going to be more likely to bleed because we know there's that vasodilatory effect. Now I've got a very cool picture here of a This is the same patient that has had a Pax volume taken pre pre-med and then literally within the next 45 minutes after pre-med.
And what you can see here is pre-pre-medication, a patient's Pa cell volume is 46%. And then post pre-medication, a patient's pac cell volume has, got all the way down to 38%. So we've got this decrease that's occurred.
The red blood cells haven't gone anywhere and that they shouldn't have gone, i.e., they're not bleeding and picked up on a bloody swab or in a suction bucket.
They're still in my patient. I've just gone into the spleen, but that's how quickly you can see that effect. Now, we talk about This thing called MDR one mutation, which we're going to cover in the next slide.
And should we avoid this, this drug with patients that are that have this MD1 MDR one mutation? Should we avoid this drug with boxes, or should we just be really care with this dose in large breed dogs when we use aramazine, should we maybe just not use this drug at all. We just have to reduce drug doses in our large breed dogs, that's all.
Instead of doing meg per kg doses, we talk sometimes in our large breed dogs about doing doses on body surface area instead. And because these dogs have, this change of body surface area to body mass, they might need a different Dose and therefore it tends to actually be this reduction in aromazine. So that effects aren't so profound.
Now care with boxes, boxes have high vabal tone. They are a brachycephalic breed, and with that they can have this low heart rate. So if we give aromazine, let's be really careful because with that vasodilation and their high high vagal tone and low heart rate, they can actually have syncope occur.
Now let's focus a little bit on that MDR1 gene mutation or that multi-drug resistant one gene mutation. So this is something we should consider in a very select few breeds that our patients undergoing anaesthesia. What we have is this normal pe glycoprotein pump, and a nice normal patient, the drug will go across the cellular membrane as you can see on the left-hand side, go inside the cell, exert.
Effect. And then we have this PGP pump, which will go right drug. It's time for you to get out of here.
You, I'm part of this normal process of metabolising and moving the drug on. And, but when we have a drug, sorry, when we have a patient that has this MDR1 mutation, which you can see on the right-hand side, their peak like a protein pump does not work as well or at all. So what happens is we that drug, it's on the outside of the cellular membrane.
It crosses into the cellular membrane, exerts its effect, but then it can't get back out again. So what happens is we get this buildup of drug and potentially this subjective overdose towards this patient. So we've got to be really careful giving our drugs to patients that potentially have this MDR1 gene mutation.
We used to just think, well, I certainly just grew up in the veterinary world thinking it was going. The border collies, but actually, it predominantly does affect herding breeds, but it's the rough and smooth coated collies that are, most predisposed to carrying these genes. We've then got our Australian shepherd, about 50% of Australian shepherds might carry this.
Our English shepherd is about 5, 15%. Our little shelties, they're about 15% as well. 15% of these dogs will carry this gene mutation one way or another.
We've got our Swiss Shepherd, our German Shepherds, they're a little bit lower down on the list. And actually the Border Collie, which is the one that I've always been more afraid of, only 5% of border collies are carrying this. So a lot of different anaesthetic drugs will affect patients that have this MDR1 gene mutation.
We think about aromazine a lot, but it can also happen with morphine, buprenorphine, and borphenol. What you can do is if you suspect your Patient may have this type of gene mutation is you can actually either do a blood test or a buckle swab test and send that off to a lab to be analysed. And typically you might hear that the breeders know that they have the mother or the father carrying this gene and they might pass it on to people who purchased the puppy.
But if not, if in doubt, have a look at your local Kennel Club website because you can find where to send the test for that specific breed. Now dexmiomidine or menaomidine. This is a wonderful drug that works at the alpha receptors.
It works at both alpha 1 and alpha 2, but it prefers highly, highly selected to the alpha 2 receptors. However, we still will get the central and peripheral effects. We get this very reliable sedation and muscle relaxation because of this.
Not like our aromazine, like will it or won't it work with with meatomidine, we tend to get quite reliable sedation and muscle relaxation. And the wonderful thing about this drug is that it can be antagonised to improve that recovery, make it faster if they're taking a long time, and, and also if there's an emergency, we can antagonise it. It does have different onsets of action depending on which route you give it.
Usually, if we give it into the muscle about 20 minutes and if we get it into the vascular space, about 2 minutes, that sometimes 1 to 2 minutes can work quite quickly. Duration of action is definitely dose dependent, but typically we can get about 30 minutes to 3 hours of sedation, and we can actually get analgesia with metatoamine as well. And we get that analgesic effect on board for about 1 hour.
Be mindful again, a sedation will last longer. So when you are doing a pain score on your patient, just think that your patient might be too sedated to respond appropriately, but they could still be feeling things. Once again, this drug is involved, well, the hepatic metabolism is the thing that's going to help remove this drug.
Let's be careful that patients that have liver disease. It's also highly lapoylic so it will cross that blood brain barrier and it will also cross that placenta into our patients that potentially are pregnant that will affect their foetuses. Effects on our patients, we can get the space of constriction.
I think that's a very big thing that scares people is the pale patient that's received Meatomidine. So that vasoconstriction occurs because of the peripheral effects on the alpha receptors. However, we get that very profound vasoconstriction causing this reflex bradycardia that heart does not want to pump into such small pipes anymore.
But this is a biphasic drug, so we get that very intense constriction and reflex bradycardia within the first kind of 2030 or 40 or so minutes of the use of that drug. And then what happens over time is that vasoconstriction will wane away and we'll still get that very nice central sedation. So we've got that peripheral effect waning away of our vasculature.
And then we still get that nice central sedation. So that's wonderful. But in the meantime, during that phase one of this drug, that really intense vasoconstriction causing that reflex bradycardia, we get something called delayed brain time.
So what that means is as we induce our patients anaesthesia. It's going to take a bit of a, a longer time for that anaesthetic drug, that propofol or that faxolone, to get to the brain to cause that unconsciousness. So we've got to slow down the administration of our induction agents when we've got melatonin on board because it's just going to take longer for that drug to get up to the brain.
This drug doesn't necessarily affect minute volume, exactly. So minute volume is how much our patient breathes in and out in one minute, and it isn't just the rate, it is the tidal volume. So tidal volume times respiratory rate gives us our minute volume, the total volume of.
That patients breathing in and out in that minute, and metaomidine doesn't really affect minute volume. The respiratory rate can drop down, but actually that tidal volume can almost double sometimes with meomidine. So you might get a respiratory rate that's about 8 or 10, but the patient remains normal Kaick because they're taking these really big breaths.
However, we've got to think that once again, this drug will be affected by other things we get with it, i.e. Opioids that cause respiratory depression.
So maybe we still do need to step in and help our patients ventilate. It can assist in thermoregulation. This is a wonderful, side effect if you like.
I'm doing that in inverted commas of dexametomidine and metomaine is because of that peripheral vaso constriction, our patients don't lose so much heat out of their periphery, so they can stay quite warm. We can see a hypoglycemia due to this decrease in insulin production, so it does work on the beta cells of the pancreas. Does this mean we shouldn't use it in our diabetic patients?
I do not think this is a reason to not choose this drug for our diabetic patients. First of all, if we can antagonise this drug, so we can get our diabetic patients back up to normal and back into the normal insulin routine very quickly. However, we will, it will affect how we read our patients' blood glucosis for that day, but to be honest, anaesthesia for a diabetic patient is already quite overwhelming.
There's fasting involved. There's maybe full, half or no doses of their insulin. So I'm not too worried about the hypoglycemia necessarily that occurs with the use of metatonadin in diabetic patients.
Metatonadine is still a wonderful drug that can be antagonised for those types of patients. It can reduce that anti-diuretic hormone, and so we will get a change in urinary output and urinary production. So once again, let's just increases.
Express that patient's bladder prior to recovery, whether they've had this or we know that opioids also affect urinary production. Now this drug can cause vomiting, it can cause vomiting, especially in cats in low doses when we give it via the iron route, we give it into the muscle. They should be really mindful that if we do give this drug intramuscular in those patients, we just don't want to vomit if they potentially have intracranial, like a raised intracranial pressure.
They've got raised intraocular pressure because that action of vomiting will cause that, pressure in the eye to rise. And if they have a fragile. Eye or a very deep ulcer, it can actually cause a lot of trauma to that eye.
And once again, if they've got this esophageal foreign body, we want to be very careful with giving this drug, especially I am. When we give it intravenously, we tend to skip right through that vomit centre in the brain and get them sedated quite quickly and they don't do it. Now atipamazole is a drug available which can be used to antagonise dexmeatominine or megatomaine.
It is an L2 antagonist. The thing is, we don't always have to antagonise metatoidine. We don't necessarily have to give it if the station was over an hour ago.
It just means that we can allow our patients to have a really nice slow recovery period. Like they would do if we had given them aromazine, which lasts for 6 hours, that you cannot antagonise. Now, if ketamine has been given to our patients, let's be really careful with the timings that we give atitamazole and the other drugs that are on board with that patient, because if we fully take away that sedation part too early and that patient's anaesthetic experience, I've still got ketamine on board.
They can have a very dysphoric, a very crazy ketamine type recovery. Just depends on how long ago the drug was given and also what other drugs are on board. Do we still leave them with a sedative, maybe a benzodiazepine.
But if we don't have a benzodiazepine, let's be very careful antagonising sedation drugs with ketamines on board. Should we be reaching for antiamazole, intra-op if our patients are hypotensive? Actually, if we have a patient that's bradycardia and hypertensive and they have melatoninine or dexamine on board, we should instead perhaps consider reaching for an anticholinergic to speed up their heart rate to improve that blood pressure, not attiammazole.
It can actually make things a whole lot worse. And we have quite a lot of evidence for this. So I'm not going to read them out in their full study findings.
I'm just going to tell you the bolded bits. So we do have a study that says it will transiently decrease the main arterial blood pressure in patients that we're trying to treat hypertension. The second study talks about giving, giving atipanazole to patients who had received dexmilaomidine when they were hypertensive.
So they already had a high blood pressure, but what it ended up doing was reducing this blood pressure by 40%. Now, we're typically reaching for this drug when they're hypotensive. So if they're already hypertensive and then we reach for this drug, clinically important arterial hypotension could ensue.
Another quite recent study of ours that says that it's ineffective at increasing the pulse rate or cardiac output in our patients under anaesthesia, and antizol can cause severe but short-lasting hypertension. Quite worrying. We've also got a study in CAT that says it does create a temporary hypotensive state and then when they are still anaesthetized with isofluoran and our last study.
Well, actually it's not even a study, it's a Noa compendium. This is in our drug Bible, a transient hypotensive effect can be seen when we get attiammazole. So let's perhaps not be reaching for that to treat our patients that are bradycardia and hypertensive under anaesthesia.
Let's instead look for an anticholinergic. So looking at ketamine, this can be used in multiple different parts of the patient's anaesthetic experience, but I've just put it under the sedative section at the moment. So ketamine, this is an NMDA antagonist, and we use it as an analgesic drug and as a dissociative sedation drug.
And how it works is if we have a look at our receptors here, we've got glutamate. Now glutamate on our NMDA receptor is an Excitatory transmitter. And it's there to hype everything up if you like.
I always remember it as glutamate. Your mates get things pumped up, get things busy, get you really hyped and excited. What happens when glutamate binds this NMDA receptor is it bumps out that magnesium you can see and allows this influx of calcium to go through the cell and send messages up to the central nervous system.
So what we do instead is when we give ketamine, we kind of bind to this receptor and where we fill that spot where the magnesium would sit so that we don't allow glutamate to, to knock out the magnesium to allow calcium to go flying through the cell and send that message out to the central nervous system. So it kind of sits in the middle there where that where that magnesium is. That's how I like to think about it.
We can give this drug as a pre-med, we can give it bolus in the surgery, and we can give it as a CRI. The thing is, it does cause muscle rigidity, so we do need to provide it with a sedative as well, just to relax those muscles so that our surgeons can operate. It can increase the heart rate and contractility, which therefore might have an effect on the patient's blood pressure, but it is not a drug we should be reaching for to increase patient's blood pressures.
That is not what this drug is designed for. A lot of people talk. But using ketamine to increase blood pressure.
It's not what it's for. It has other side effects. And it can increase intraocular pressure as well.
Let's be careful if our patient has a fragile eye, and it can increase intracranial pressure. Does that mean we shouldn't be using it in patients with head trauma because of its actions, reducing glutamate, being having that excitatory effect as a transmitter. Actually, if we give ketamine, there's some promising evidence now that we can, Have a more of a neuroprotective property to that central nervous system that's damaged instead.
It can cause apnotic breathing, that just means our patients might breathe in quite a lot, and then they hold their breath for a bit or they just get rid of all of their CO2. So it can happen, but it, I tend to not see it too much. It can be, it's excreted unchanged in cats via them urinating it out.
So let's just be careful with cats that have a blocked bladder. Looking at propofol and Alexxolone, so our and our induction drugs, these drugs will work on our GABA receptor. If you think about GABA, I always think about all of the A's in the word GABA, and I kind of go GABA.
So you feel really peaced out when you say it, it's the GABA. Receptor and that GABAA receptor that will control the majority of the inhibitory signalling in the central nervous system. So that means if we can inhibit signals going up to the brain, we can induce this sedation or unconsciousness by using drugs at this site.
Putting those drugs side by side, they both cause unconsciousness, which is what we want, and they both do have similar other properties to our patients. They can cause vasodilation. Both of these drugs can do that.
And propofol can actually decrease the heart rate as well, leading to a hypotension. But alfaxolone actually preserves something called the Barrow receptor reflex, so the pressure receptor reflex. And what we have instead is this vasodilation that occurs.
We can't help that. But the barrow receptor sense that vasodilation and they go, oh gosh, I need to increase my heart rate to maintain normal tension. So actually, you will get an increase in heart rate when you use alfaxolone.
And this is a Great thing. It's trying to preserve a patient's cardiovascular system and cardiac output. So this is a really nice drug that we can use in our patients that do have heart disease.
They do both have respiratory effects, potentially there's a little bit less with alfaxolone. And a big key point with propofol is we want to avoid repeated doses in cats, and they will end up with something called the Heinz body anaemia due to the phenols and propofol. So when we say Repeat doses in cats, we mean doses greater than if we were to anaesthetize the same cat every day consecutively for 3 or more days.
We don't want to be reaching for propofol. Now you might say, Well, why? Why would that actually happen?
This could be a blockburn cat. It could be a cat undergoing wound management. It could be a cat that's having daily bandage replacements for a fracture or something like that.
It absolutely can happen. Let's be careful using propofol repeatedly in cats. Let's reach for something else instead.
Now alfaxolone does cause a lot of twitching, even whilst the patient is under anaesthesia, but definitely leading into the recovery period. Let's make sure they've got a sedative on board. They can twitch their pores and they can flick their ears as well.
And I actually, when I first used this drug, was so overwhelmed by my patients recovery experience. They were twitching. I actually thought they were having a seizure, but it is in the data sheet that these patients need to recover in a dimmed, calm, dark environment because of the twitching that can occur.
Now, if we have a look at our benzodiazepines, midazolam, and diazepam, they work in the same type of receptor that propofol and alfaxolone work at. So they work at our GAA receptor. And we can use these drugs as an anticonvulsant, but we can also use these drugs in the pre-medication or co-induction phase to provide anxylytic effects and also sedative effects.
The thing is with the sedate. It's not very effective in in healthy cats and dogs. It's a good sedation choice or coinduction drug for the very sick, the very old, and the very young.
But we still will get muscle relaxation with this drug in those patients. It means we might not get such bad cardiovascular effects as if we were to anaesthetize the very sick, very young, very old with aromazine or meatomidine. Side by side, they, they do have some similar properties.
Midazolam does not have active metabolites, which is why we can end up giving this drug in a CRI format. Our diazepam does have active metabolites, we don't really want to be given this drug. As a CRI sedation, yes, it can provide sedation in the very young, very old, very sick.
And midazolam does have a short duration of action. So the duration of action is about 1 to 4 hours, whereas diazepam has a duration of action of about 4 to 12 hours. You can give midazolam as a CRI like I said, we wouldn't be doing that with the diazepam.
Both of these drugs are highly protein bound and involve the liver metabolism. Let's be careful in our patients that have liver disease. Let's be careful in our patients that potentially have these proteins because of that.
We will otherwise have more drugs floating around causing an effect. Now, depending on their chemical structure. Midazolam has an imidazoline ring and diazepam has its benzyne ring.
So what this means is when we give midazolam in the intramuscular route, once that drug reaches the body's pH, this ring closes and exerts its effect, which is why it allows us to give midazolam IM or IV. It's got this ring structure that will allow the drug to change within the body's pH and be used across many different access points, whether that is intramuscular, whether that is intravenously. Unfortunately, with diazepam, we don't give this one intramuscularly because of the way the drug ring is structured.
Both of these drugs are light sensitive, so they do need to be kept away. Sorry, diazepam especially is very, very light sensitive. If your midazolam comes in one of those brown vials, keep it away from the light as well, but typically, midazolam doesn't end up being light sensitive.
And the wonderful thing about these drugs is you can antagonise them as well. Side by side, the effects on our patients, minimal cardiovascular depression, that's why we like it in our very sick, very old, very young, and but there is some respiratory depression as well, but this is a lot of anaesthesia drugs. Now, having a look very quickly at anticholinergics because this used to be a drug we added to pre-med a very, very long time ago.
Why? Because of its actions right down here at the cholinergic side of the autonomic nervous system. So our cholinergic receptors, we've got nicotinic receptors and we've got muscarinic receptors.
We used to use anticholinergics such as atropine or glycopyrolate years and years ago when we were using ether. Which increased salivation in our patients, and we didn't want to increase salivation, so we would give anticholinergics to try and dry up all of these, the salivary dangerous and parietal secretions. We don't use those drugs anymore, but instead we might reach the atropine or glycopyrolate if we have a patient that has now got these effects on the M2 receptor.
So this is our musculinic receptor. So things like opioids or metaomidine causing this decrease in heart rate, this decrease in AV conduction, maybe we've got a, an AV block. We might now need to reach the atropine and glycopyrilate because of the sedation drugs or pain relief drugs we gave in the pre-medication just to try and bring that heart rate and blood pressure back up.
Side by side, unfortunately, it binds to both, well, all M1, M2, M3 receptors. We do get these other types of effects that I've just showed you here, but we predominantly want to be using them in anaesthesia for the M2 effects on the heart. The thing about atropine, it's very cheap, it's an emergency drug.
We've always got access to it. And glycopyrolate, it's quite expensive, but the thing is that I like glycopyrelate a lot more. So let's just put them side by side and I'll show you why.
Atropine is this nice emergency drug that has its onset of action in 1 to 2 minutes. So that means a very slow heart rate is going to start beating very, very quickly in a very short amount of time, whereas glycopyrolate takes it a little bit longer, so it's quite nice. We do have a short duration of action with atropine, about 1 hour, whereas glycopyrolate is about 2 hours, so it's going to get us through our patients anaesthetic experience.
We can get a paradoxical bradycardia occurring with both drugs. So what that means is we try and treat a bradycardia and actually initially with potentially low doses, and we can see the heart rate get a lot worse. Now this just means we might have to repeat the dose or just give it a good minute.
Both of these drugs will dry those secretions, which is why they used to use it decades ago. We can get a bronchodilation using these drugs. It's not really significant.
You won't see a change much in your patient's knograph. And atropine does cross the blood-brain barrier and it will provide essential effects causing that, dilation of eyes, whereas in glycopyrolate it doesn't cause that. Looking at our local anesthesias, we give our local anesthesias as a nice compliment to our patients' anaesthetic experience.
Although we pre-medicate our patients with analgesia, this is just dulling the effects, saying, don't worry, brain, it's not that painful. Whereas when we use local anaesthesia, this is the only true analgesia. This literally stops pain reaching the central nervous system.
It does this by Binding onto those sodium channels, and it then prevents that cell from depolarizing. So when we are sending that message up to the brain, so when we use local anaesthetic with other drugs, and it actually will allow us to reduce other types of opioids and sedatives. Therefore, think about that Long Island iced tea, reducing the amount of the high doses that we might think we need, and therefore, the dose dependent side effects.
So it's a wonderful Thing that we can splash, we can bathe around nerves, or we can put in to have complete regional anaesthesia. Now, these are our most common agents, the lidocaine and buppicaine. Lidocaine has quite a quick onset and a short duration of action, really good for things like castrates, and buppivacaine has a slower onset of action, depends on what you read, but about 5 up to 20 minutes, it needs to be there before you introduce that painful stimuli.
Perhaps taking teeth out. But it does have quite a long duration of action. You can get about 4 to 6 hours out of it.
The thing is, we do not want this drug at all to go intravenously because it can be cardiotoxic. Lidocaine can go intravenously, but regardless of which agent we use when we're doing a local block, let's aspirate when we're close to the nerve, make sure we're not by a vessel, and then inject and instil that local anaesthetic drug. Now I've talked quite a lot about anaesthetic drugs reducing MAC or minimum alveolar concentration.
I just want to quickly focus on Mac. This will describe the potency of a volatile agent. And what this is, it's a very lab.
Created thing that was done decades ago as well. And what they found was they gave, when they were using a particular volatile agent, they gave a percentage number to that volatile agent where they found that purposeful movement didn't occur in 50% of that patient, 50% of the patients. When that vaporizer was at a specific setting.
So let's say they had 100 dogs laying on a table anaesthetized with isoflurane. With their isoflurane being at mack of, well, they found out that the isofluorine in dogs was at 1.3%.
Then 50% of the patients moved and 50% of patients did not move. So that's all MAC is. It's, it's this fine point that we've found with volatile agents with 50% will move and 50% will not move when we introduce a painful stimuli.
What this means to me as someone who monitors anaesthesia is it doesn't matter what vaporizer is in the theatre when I walk in. I will understand the Mac and go, right, I can understand how to use this vaporizer and what setting I should set it to. So we books will say, if you want 95% of your patients to not move with the volatile agent, you take the volatile agent Mac and times it by 1.5.
However, we use a lot of other MAC sparing drugs. Literally everything is pretty much Mac sparing except for like non-steroidals. They don't have a big Mac sparing response, but everything else, melatoninine can reduce your MAC by 70%.
So just by having your volatile agent. And a normal patient without melatonin at 1.3%, when they have metatonamine, you can go way down to like 0.9%.
Now, we use match readings on our multiparameter if we have agent monitoring on what the patient breathes out. So you'll see in the corner of some multi parameters, it tells you about the concentration of volatile agent that patients exhaling. What we're doing with that information is we're assuming what's in their alveoli must be what's in their blood, which must be what's in their brain, keeping them anaesthetized.
Now when we think about the Mac for different volatile agents, and especially describing potency, you can see isofluorine is quite potent, the Mac in dogs is 1.3, and the Mac in cats is 1.6.
Instead of fluorine, it's less potent, so we need more of it. To keep our dogs anaesthetized and our cats anaesthetized, we typically need over 2% on a vaporizer. Dogs are about 2.3%, cats 2.6%.
No one's using des fluorine anymore, but I hope not too much because it's it's quite bad for the environment. However, this fluorine, just for comparison, isn't very potent and we can have a delivery of up to about sorry. 8% just to try and keep our patients still.
Now minimum alveoli concentration can be increased, we can have this increased max. And our patients that have a fast metabolism. So paediatric patients, hyperthyroid patients, even our hypothermic patients, it can be decreased in patients that have geriatric, that are hypothyroid or hypothermic.
So we need to turn down the volatile agent. We know we have a lot of max sparing drugs available to us now. Last but not least, we've got non-steroidals, and we have so many non-steroidals available to us, it's really hard to keep up.
But I just want to point out where non-steroidals actually work. So this is our pain pathway. We've got transduction, transmission, modulation, and perception.
Right down at the level of transaction is where our drug, our non-steroidal drugs are working. The transaction is when we have some kind of insult to that tissue, and our nose receptors will translate that information into an electrical stimuli and signal to go up towards the central nervous system. That happens in our transmission process.
It then gets to the spinal cord and it's modulated. Should I send that message up to the brain and tell the brain that we perceive pain, or should I not? But right down at the tissue injury level is actually where our non-steroidals are working.
So you might be familiar with something called the inflammatory soup. So when the cellular membrane is injured, so when that tissue is injured or damaged, it leads to this activation and release of these inflammatory mediators, which create quite an acidic environment which we refer to as inflammatory soup. Now this inflammatory soup, this will hypersensitize the no receptors and it will cause hyperalgesia and get That message all the way up to the brain.
We are really painful in this particular area, send, send lots of inflammatory mediators here to make it all dilated, full of blood, all red and very painful. But what and where our non-steroidal drugs work is actually, if you follow that noxious stimuli up to tissue damage, And then you can see aracheddonic acid there. Now, acheddonic acid is involved in the formation of the leucotrines and the prostaglandins, and our non-steroidals stop this breakdown of acheddonic acid into prostaglandins.
So that's where it works. It's there to try and reduce that inflammatory response and therefore reduce pain associated with that. Now, there's always this discussion, should we give, non-steroidals pre-surgery, during surgery, or post-surgery.
We do want to be careful giving it, if we're anticipating that our patient might bleed a lot or become hypotensive. But in all honesty, we, by understanding how this drug works, we kind of need the tissue damage there for the non-steroidal to work. If we give a non-steroidal to our patient and there's no pain or inflammation, it's just kind of I don't know.
I always think about it as floating about. It's not really got anything to do yet. There is no sign of tissue injury.
The moment there is tissue injury there, those inflammatory mediators are released, it goes towards that area. But for me, I also feel that I can wait until my patient is safely out of their anaesthetic experience. I'm no longer hypotensive or at risk of bleeding.
And I can give the drug. And they will still have that pain relief effect very, very quickly, that anti-inflammatory effect very quickly. So I don't think you'll even find a general consensus to get it pre-pei or post, but I don't mind giving it postoperatively because as soon as we do give it, it's going to find that tissue information, it's going to find that inflammatory soup, and it's going to work pretty quickly.
So that's everything that we have covered. We've gone to what is anaesthesia, it is Greek but without sensation and hopefully reversible, otherwise it's euthanasia. We've had a look at some of the common anaesthetic drugs and although we looked at things that aren't necessarily what we call sedation drugs.
And it could be a volatile agents or our induction agents. How we still pre-medicate our patients and the effects of those are still all intertwined and holistically affected. And then we've touched base on the pharmacodynamics, and how those drugs work in the body.
