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Hello, everyone and welcome to our um talk today on Basic Anesthetic Pharmacology. Uh My name's Sue and we have Akan, he's gonna probably rep pronounce that for me because I think most of you know who are regular here. I am really rubbish when it comes to pronouncing names, medical names, all of that kind of thing. But anyway, he's a consultant Anestis and he's working at the University Hospital of Leicester. So we're gonna be doing something a little bit different today. Um For those who of those of you who have been to some of our other events, you will have seen that. Normally we just use the chat for questions, we're gonna make it a little bit more interactive. And if you would like to come up here to actually answer a questions verbally rather than typing, I would love for you to just pop join in the chat box. And then I'm gonna invite you to come on to the main stage, you will stay with your mic and cam off. And then if a ask the question that you want to answer, you can turn your mic on and answer it verbally rather than typing away. OK. You can do that at any point throughout the event. If you want to join the stage, just poo keep your mic and ca off, you'll join with your mic and ca off anyway. So just leave it like that. And as soon as there's a question you want to answer, you can turn your mic on and answer that question. All right, it is gonna be interactive. We do want questions in the chat as well. So if a says, does anyone have any questions, we want you to be there to answer them? All right. Um As always, you'll get a feedback form at the end of the event and your attendance certificate after you've completed that feedback form will be on your medal account. So without further ado, I'm gonna hand you over to ac and please put join if you want to join the stage. OK. Thank you ac. Hello, good afternoon. Uh or whatever time it is uh a day it is wherever you're watching this. Um So my name is A K Ran. I am uh an assistant Leicester. Um I'm gonna be talking about talking to you about um basic anesthetic pharmacology. I'm going to try and make this quite clinical and less about the numbers and less about the nitty gritty, but I will put those on, on the screen for you as well just so you have that background and it's more about when we're going to do what, what we're going to try and cover is, um, initially, I tried to put quite a lot of different groups of drugs in here. Um, but I thought what we'll do is try and focus on the, uh, how we use things like IV induction agents, inhalation agents, um, anesthetics and muscle relaxants and go through them in detail. And then maybe we can do another a second session looking at, um, you know, painkillers, opiates, um looking at local anesthetics and other things like that, which may or may, may, may, may or may not be useful to you. Um We're going to focus a little bit on pharmacodynamics. So what the drug does to the body and it's the side effects and why you would choose one drug over another. Um And the situations where you might want to use that. Um I won't do too much about pharmacokinetic to say what the body does to the drug eliminations and things like that. Um Apart from where it might be relevant to how you use it. So that's the, that's what we're going to try and do today. Um What I what, what, what I'm gonna try and do today is again, try and make this interactive, trying to get you to um uh ask questions about questions you have about how you might use things in your practice. Um Some of the questions you might have about interactions or um things you might see rather than uh, uh, just me talking at you. I'll try and give you an idea of how I do it in my practice. Um, it's not the only way it's certainly, um, uh, it, it's my logic behind how I do this rather than, uh, being the definitive answer for these things. So please join in if you have any questions or have any queries about, um, why you would use one drug over another or what combination of drugs to use, um, in different scenarios, then please, er, join in, ask questions in the chat or come onto the screen and join in as well. So we're gonna start with the intravenous induction agents. Ok. So these are, uh, what we use for, uh, putting people to sleep in a, to start with. I'm gonna focus on the four that, uh, we, we, I most commonly use or, uh, commonly used around the world. Um, so we're gonna focus on propofol, thiopentone, etomidate and ketamine and we'll talk about why we'd use one over the other situations where one is useful, uh, the situations where we don't use them and, uh, and go from there. So if we start with Propofol, the most popular drug that's used in the world for induction and generally anesthetics, um, it can be used, uh, as an induction agent. Uh, it can be used for maintenance and, uh, it's often used for sedation. Um, it is, it comes as a, as a white, uh, liquid, it, it contains um uh it's, it's kind of a I in a in a fatty emulsion may also with egg protein. Um The dose, the official dose is 1 to 2 mgs per kilogram. But for most people, it is you give it to titrate it to effect. So in the emergency situation, you might need more because of um people's anxiety, adrenaline increases and so you might need more than that. Um You may need less in the elderly populations and you can use it as a co induction agent with various other drugs as well, which we'll talk about in a bit. Um The, the key things that I I probably probably should mention are that um propofol, the, the kind of the medium that it comes in. So that that white fatty uh liquid that it kind of is, is emul in means that it is a, it's really quite um a good culture for bacteria. So um you really should use it, you should only open it and use it straight away. You shouldn't really kind of um open a vial and leave it on the side and use it later because it can, you can get um bacterial growth quite quickly within a few hours. So that's the main thing. Um we do use it in Children. Um a lot of the pediatric intensivist and, and some of the uh traditionally we try and avoid propofol for long prolonged use. So you wouldn't use it for um keeping people, keeping Children asleep on um pediatric intensive care units because of the of of because of prop syndrome that you can get. Um but I we use it too as an induction agent in Children as well, but you do need higher doses, ok. In terms of its effects on the body, um it causes uh vaso dilatation. Um that's a combination uh which then leads to a decrease in systemic vascular resistance and a subsequent drop in BP. And that's dose dependent. Um It, it is, it does cause apnea. So giving too much GERD does uh cause apnea. Um but, and it also quite usefully sup suppresses the laryngeal reflexes. So it's very useful when you're giving propofol and you're using supraglottic airway, an L MA or eye gel or another type of supraglottic airway. Um Propofol really does come into its own there compared with some of the other induction agents. Uh And it, the Broncho Bronchodilator, um you get a very smooth induction, it's a very gradual um process of induction rather than um some of the other drugs. Um it does reduce intracranial pressure, it does reduce sort of your blood flow. Um It is anticonvulsant. Um but one of the side effects can be that you can get um tremors or jerky movements when they wake up afterwards. So for a while, it was um you try to avoid it in people with epilepsy. Um But that's primarily because of issues with driving afterwards. Um So in the UK, if you have a seizure, you're not allowed to drive for 12 months. So the reason why we avoided it um for ep epileptics is we didn't want to misinterpret um those kind of jerky movements that they can get when they wake up as a seizure to and then affect their ability to drive. So that's the main reason, but it is an anti convulsant and it's also a very good antiemetic. So, if you are looking for somebody with, you know, has a lot of postoperative nausea and vomiting, then some sort of TIVA technique or total an intravenous anesthesia might be useful for these patients and it is, it does sting when you inject it, particularly if it injecting it into small veins um or small gauge cannulas. Um So different people have come up with different ways of mitigating that. So that can be either by um injecting it, mixing with some local anesthetics, lidocaine in with the Propofol or giving a bit of um like a half a mil of lidocaine prior to giving the Inj Propofol seems to help with that, but essentially bigger cannula, bigger um veins tend to tend to not cause too many uh pain issues or pain on injection issues. So that's propo as said, it's the most commonly Woz one, it's probably the one that most people are familiar with um to, to use. Uh mhm The next one we're gonna talk about is thiopentone. Uh Thi thi sodium thiol, there's lots of different names for it, but it's the same, um, same drug. Um, here, I it's a thigh barbiturate. It's used for induction. It's also used for sedation or in on the intensive care units, uh particularly in stage epilepticus because it produces a burs suppression eeg. Um The, the dose is, uh I was always told it 3 to 5, but the book says 2 to 7 mg per kilogram. Um And the, the, the difference with thone versus propofol is whereas propofol, you get a very gradual status, smooth induction. Whilst I pen 10 is smooth, you go from being awake to asleep. It's a very distinct cut off point when you're going to sleep. And so that's why it's very useful in the past for rapid sequence inductions for people. You are at risk of aspiration um from of gastric contents. It's gone out of favor in the UK. Um Mainly because of the fact that we don't use it very much because, and we lost familiarity with it rather than it being anything bad about it. Um So most people use propofol for their rapid sequences rather than thin. There are still a number of people that use thi um it and that's because of the next thing which is it is a negative in pro trope, it decreases cardiac output and it decreases systemic value, vascular resistance and decreases BP. And so what was happening was that um you, you, you kind of pre calculate the dose and you'd give it under uh what you think would be, be the right dose. Uh And so you often over, over egged it and, and gave too much and you get a profound drop in BP in those patients. You were very worried about, you often get you under dosed and uh you end up with a higher incidence of uh awareness under anesthesia uh in those emergency patients. Uh And it's completely, it works completely, you know, really good drug. It, it's really well in those, if you use it regularly. Um what happened in the UK was we didn't use it regularly. And so people's familiarity wasn't there. And so we got to a point where you don't use it intermittently and that's when you cause problems. Um and we had, you know, people being overdosed and having profound hypotension or under dosed and being accidentally aware. So that was the problems and why it's not used as much at the moment. Um It does cause apnea as well. It um you get prolonged respiratory repression. So, you know, if you, if you have a short procedure, you can get a bit of a hangover effect. Um whereas Propofol you can kind of, you, you come out of it quite quickly, smoothly, but you get a come out quite quickly and um when you emergency is much more clean with thin, you can get a, a kind of a prolonged hangover. Um uh which is another reason why, you know, for short procedures, it wasn't really used. It's good for the emergency, big big cases. Um It does, it is a very smooth induction agent. It does decrease intracranial pressure and through blood flow and it is the, the anticonvulsant, it because it stops, um, it causes bur suppression on the eeg. So they're, they're the two basic uh drugs that we, that um are used most commonly um or have been used most commonly in induction. The next one, it's not used in very many countries at all. So, etomidate um is, is primarily an induction agent. Um The, the dose you use is 0.3 mg per kilogram. Um I think, you know, I'm not a cardiac an this, it is, it is using um most commonly has been used in cardiac anesthesia. It is banned in lots of parts, parts of the world. Um uh and I'll come onto the reason why in a second. Um it is the other white drug. So, um so Tomo can either come in a uh in a fatty emulsion uh like propofol. So it looks very similar to prop or it can come in a, in a clear solution as well. So, um there's two different forms that you can buy it in um the benefit and then why it's used in cardiac uh has been used in cardiac anesthesia before is it's very stable cardiovascularly. Um It gives you, um my spelling is appalling on this. Uh It gives you very um stable in uh induction with um no, no drop in BP. Um It gives you transient apnea and you get, you get reduced tidal volumes and reduced uh respiratory rates. Um you can get coughing and hiccups part of that. Uh and you sometimes get involuntary muscle movements and can get epileptic form activity on eeg. Now, the reason why it's not used um uh very much at all is that it impairs the steroid synthesis pathways um even after a single dose, um it, it was, it used to be used and uh in cardiac anesthesia and particularly in the POSTOP um maintenance. So if you want to keep somebody asleep on a on a cardiac ICU S, they, they, they initially used to use omid because it was very stable. But then they found that had severe um consequences to the steroid synthesis pathways, but even a single dose can impair steroid synthesis though it's not very clear how much of a clinical significance that is, but most people aren't willing to take the risk because there are other options you can use and other ways of inducing somebody um that's in a cardia stable way without having to use. Cont OK. And then the final one I'm gonna cover uh within the intravenous induction agents is ketamine. Um Its use is, is an induction agent. Uh It can be used for analgesia. I've certainly used it for procedural sedation. Uh and it can be used for uh sta status asthma. So, you know, people in um acute uh asthma attacks, um the dose for induction is 1.5 to 2 mgs per kilogram. Um I have used it in procedure station um in so in the emergency departments, uh particularly in Children, uh where you can use a half M GM per kilogram dose titrated up. Um And you get um uh you can give kind of manipulations or um uh putting back dislocations, things like that where you need to do any kind of orthopedic manipulations. It's quite useful for that kind of stuff or uh or very simple procedures because it has got some analgesic properties as well. The main, I guess the main side effects are that, that kind of limits its use is the emergency delirium and hallucinations that you can get. People tend to see, they say they see spiders on the wall or they can get hallucinations, but that can be minimized by um by putting them in the dark room or by the use of some sort of benzodiazepine such as midazolam or diazePAM can kind of reduce the amount of, of emergent delirium hallucinations. The reason why it's really useful is that it increases the heart rate, increases your BP and increase increases sympathetic tone. It's, it's a respiratory stimulant. So they keep breathing um while you're using it. So it doesn't unlike Propofol where if you give too much it'll stop them breathing. Ketamine doesn't do that. Um But it does increase your intracranial pressure. It is a favored drug for prehospital medicine. So, uh if you need to intubate somebody uh in, in a, in a, in a um in an unfamiliar setting or an awkward position or with limited resources, then ket is really useful um because it is a respiratory stimulant and they don't stop their breathing and they don't suddenly drop their BP and heart rate. So it's really useful for that situation. Um My, in my practice, um because I don't do prehospital care, I tend to use it for um the uh hypervolemia shock. So patients who have bled severely trauma, um things like that where they, they have no circulating volume and therefore any small changes in the system, systemic vascular resistance means that they can kind of significantly um decompensate and um and arrest. So, um yeah, trauma, uh aneurysms, um aortic aneurysm ruptures um in gynecology surgery, we've got ruptured ectopics, things like that where they're hypovolemic. Um but they need an anesthetic to stop the bleeding. That's when I use it most commonly. Um in terms of it and a lot of people use it, use Midazolam as a co induction agent um to help with the emergency delirium hallucinations. It also means that you kind of reduce the dose of it. Um in terms of uh it is a slower induction agent. So it takes more than the one on brain cycle to induce. So you have to be a very patient. Um It's not, you can't do a true rapid sequence with ketamine because on set time, um it can take up to 90 seconds to, for it to, to work. Um So you have to be careful with that though. It can be used. Im So I have used it um for patients that are very agitated, who uh who haven't got IV intravenous access. Um I've done Im Ketamine injections to, to calm them down, take the edge off, things, reduce the agitation before giving them a AAA true, a different type of anesthetic. So whether that be ketamine or that be propofol depending on the situation. So that's what I tend to do with ketamine. So that's the IV drugs. Um Can ketamine B missus for neonates for infants? Uh anesthesia induction. Um I, I've used it in Children um and I've used it in infants for, for procedure cessation. Um I've not used it in, in neonates. Um but I think it has been used, people do use it in, in um I think it is now becoming more popular for, for um on PICU for induction of emergency anesthesia um rather than propofol. Um and certainly not any other drug. So it has been used in, in infants certainly. And I'm not an expert in the. NH, so I wouldn't be one to tell you what the latest, you know, uh rationale is. Um, when I last did neonates, um they use very little uh induction anesthesia. They, they often um gave um Midazolam morphine and then a muscle relaxant. So I wouldn't, that wouldn't be my, my um choice of anesthetic. But um that has been what's been used in the past. Um, but certainly on PICU they, they, they do like ketamine, so certainly for infants and Children, um it can be used. Um I would say that um most of my pediatric anesthetic colleagues uh for routine anesthesia, anesthetic induction. Use propofol or uh use, yeah, use propofol. Um To be honest, I hope that answers your question and shifting slightly to er, if nobody else, any questions on, on um IV induction and I'll talk about some of my, you know, combinations that you can use for the, for the other drugs in a bit in different scenarios and we can come through, talk through some scenarios, but I've got three sections where we're going to go through the drugs and the rest of it is a bit more open in terms of what we discuss. Um So inhalation agents, um they all tend to be halogenated ethers, they all to different degrees cause myocardial suppression, they all cause decrease in systemic vascular resistance. Um And they all cause a reduction in tidal volumes to some degree uh and they increase cerebral vasodilation and cerebral blood flow to a degree. So that's common across the whole board. Um I, I've kind of kept it quite broad um because um we'll talk about the individual drugs in a second. Um uh I, I, I'll come to the best IV anesthesia in a second, depending it, it depends on what combination, what is uh there. Um So Halothane, the generic effects um are the CNS effects are generic. So it's the same as with all the others. Um It does cause a bradycardia and it can cause um increased sensitivity to, increases your myocardium sensitivity to uh Cine. So adrenaline uh and so you can get quite a lot of rhythms because of that if you're not careful. Um And the main issue with Halothane is because it's primarily eliminated or 20% of it is eliminated by the liver. It can cause pa toxicity and that can be very, from very basic to filament to complete liver failure because of that. Um And it's thought to be some sort of immune related response to the metabolites of Halothane rather than anything specific. And then um it is so what they try and say what they suggest is that if you uh you shouldn't have a repeat Halothane anesthetic if you've already had one within six months. So that's what they say. Halothane. It is traditionally the, the drug of choice for um inhalation inductions. If you can use it. So we don't have it anymore in the UK, but it was the drug on which um inhalation induction was kind of designed for um isoflurane um is. So Halothane is a very slow induction agent. It takes a while if you can use it for induction, but it does very, it's a very smooth induction agent and you can get quite deep uh relatively easily. Um whereas isoflurane um is, is an airway irritant, so it can't be used for induction. It does cause bronchodilatation and it has been used in an acute asthma. And there is uh two things with isoflurane. It, it can cause coronary steal syndrome, so it can cause preferential blood flow in your coronary arteries to go away from any narrowed areas. Um But it has got some benefits um in terms of ischemic preconditioning, which means it's quite useful for kind of anesthesia. Um OK. It's so uh again, with neur anesthesia or anything where there's any uh concerns about um intracranial pressure and cerebral blood flow, it does increase uh cerebral blood flow but only uh when your levels of grace in one mac. So below one mac, um it doesn't seem to have the, the same impact. Um but it's still used um quite commonly uh enflurane. Um uh it causes tonic clonic muscle activity and EJ changes. It also increases your catecholamine sensitivity to myocardium and cause a bronchodilatation. Um It's, it's not, I I've not seen it used for many years now in the UK. But um I'm not sure what, what, what options people have in, in other parts of the world. Um I would say the sevoflurane is the most commonly used inhalation agent here. Um It causes bronchodilatation but without many of the other effects and does cause myocardial depression and reducing BP. And what you find is for those who are asking for about um unstable patients is that there are lots of different ways of in, in inducing somebody. What you find is you do a beautiful uh induction which is very cardiac stable, whatever combination you use and then you turn on the sevoflurane and then they have a massive dump in their BP. So you have to be very gentle when you, when you're inducing these people and build the sea flame really gently and just keep quite low. Whilst the effects of your induction agents are wearing off and then build up if you need a longer stay. And hopefully, by that time, you'll have got some, some sort of other access and maybe even start some sort of um an adrenaline or some other something else to help you or resuscitate in a different way. And so what I found most commonly is that, you know, there are different ways of doing kind of hypervolemia called trauma patient inductions and then you kind of turn on your sevoflurane or whatever um uh inhalation agent you choose and if you go up too quickly, then you get AAA kind of quite a precipitant drop in their BP. And with Desra A des is being withdrawn from use in most of the world because of its environmental implications. Um, the benefit for Desra was it, um, as a short offset time? So you, if you have a long procedure, it doesn't build up very much, you turn it off and quite soon they wake up. Um, but that difference between Desra siva flames only about three or four minutes, even after a four or five hour operation and it does cause airway irritation. It causes, um, it's not, the books don't have it as, as causing this, but in, in my practice when I was using it many years ago now, um it, in certain, particularly younger patients, it seemed to cause a tachycardia, um which in those patients, which you were, you know, either cardiac problems or had problems with um uh hypervolemia where you don't want tachycardia, then that was, you know, you end up, um become the tachycardia, became a diagnosis of exclusion. That's where that comes from. Now, in terms of um answering some of the questions before I move on to the next topic. Um The best IV anesthesia, it depends on the situation. There isn't, there isn't really, um, as I said in prehospital care, um where, which is probably the most um similar scenario to what you're describing. Um Ketamine is probably the most commonly used. Uh because, you know, you do, if you use a bit bit of midazolam ketamine, you get a very straightforward anesthetic uh induction. Um But you don't get the, the kind of sudden drop in BP, you, they can keep breathing. So you don't have, you know, you can circumvent some of the airway problems. Um uh and you can then take it from there and that's why they, they use it in that situation. Um Because of, because of that um for the unstable trauma patients, um it depends on the situation if they're hypovolemic and that's the cause of their um instability. I prefer um ketamine um uh rather than todate, we don't use etomidate very much in the UK at all. Um For, for septic patients, I would, I tend to use a high, high opiate technique. Um So you can either put, get a bit of Midazolam, a lot of opiates and then a small amount of induction agent. Um So, you know, for, for me, uh we have fentaNYL is, is our, our fentanyls are, are kind of opiate of choice. Um So I might use, you know, the standard dose uh for AY is probably a milligram. I might use two or three mg or I might use instead of 100 mics of fentaNYL, I might use three or 400 mics of fentaNYL. Um You wait some time you give three or four mils of uh of propofol. So 30 to 40 mg of propofol and give you muscle relaxant and that tends to give you quite a cardiac stable um uh induction. Um Ketamine again, I use it my in the trauma patients in the um uh in the, in the, the the the kind of bleeding patients. Um because I think that gives you a nice stable induction as well. I don't tend to use atom because whilst you can give them a, a nice stable induction, the the the kind of the the impact on steroid synthesis while it might be outside of, we don't follow them up. We don't really know, fully understand it. It means that um you can cause more problems because that steroid synthesis impairment later down the line. So that's why I don't, we avoid omid, lots of other Western countries don't have accommodate at all. Um in terms of using induction agents with, with others. Um As far as aware, there's no, there's no particular uh issues I would, I would say with, with any of the catecholamine, sen sensitizing um inhalation agents. Uh You'd want to avoid it with anything that will cause uh surges in BP or, or surges in um uh a circulating adrenaline. So, you know, I wouldn't use Halothane or enflurane in a trauma patient because what would then happen is that um if you don't have to give no adrenaline or something like that, you can then set them with arrhythmia. So with the unstable patients, um I would probably try and avoid halothane enflurane. Um mainly because, um of, of what you might end up having to give them to maintain their BP because all the other things that are going on whether, because they're septic or whether because they're um unstable from a cardiac point of view, um because that sensitivity, um I say, well, we don't use Haan and here, but I know it's your default in, in lots of parts of the world. And you just have to be very careful when you're giving um other drugs to compensate for um uh the cardio instability if, excuse me. So for example, if you're using Halothane, you titrate your adrenaline or adrenaline very carefully because you know that they're going to be more reactive to it. And then finally, we're gonna talk about muscle relaxants. Um Now this is, this is where there's lots of interactions. Um Now suc metho is the probably the cheapest and one of the, the, the most commonly used um muscle relaxant around the world. Um You, you get 0.5 to two mg two mg per kilogram IV or you can give it to IM 2.5 mg per kilogram. The reason why it's one of the best is because it's got the, the fastest on set time uh between 30 seconds to a minute and it takes 2 to 20 mi 20 minutes as an offset time. So that's the, the uh the benefits of it. Um The kind of main issues with it are that it can cause bradycardia. It so depolarizing masic uh muscle relaxant gives you fasciculation. So you get the kind of the twitching, but you get quite profound myalgia, particularly in young patients. Um It's, it's kind of role is in rapidly inductions in unstable patients. Um but it can increase in thoracic pressure. It can cause a little bit of high hypotension. It's got a quite a high um anaphylaxis rate. Um and you can't get repeated doses because it has less effect because it has tachyphylaxis. So they're the kind of more generic ones. Obviously, there are people that haven't got. So it's metabolized by um plasma cholinesterase and you can get acquired and uh genetic um uh deficiencies in plasma choline. So the, the, the genetic ones give you susy apnea um and you, you can get that tested. Um but you can get quite prolonged. So, you know, it ranges from rather than being, you know, 2 to 10 minutes, it can be 2 to 3 hours to 24 hours where they need to be ventilated because they're profoundly paralyzed and, and the, the um the muscle relaxation hasn't worn off. It also is a trigger for malignant hyperthermia, which, and it's the only IV drug that does that all the um inhalation agents can be a trigger for malignant hyperthermia as well. I've left I've left the last side effects to last because it is probably the reason why suc really isn't used as much as it used to be. Um It's because of the hyperkalemia aspect of it. So you've got to be careful in patients with a renal failure. You don't want to use it in patients with um recently recent burns. You uh have to be careful in spinal cord injuries. You've got to be careful in lots of neuromuscular disorders because anywhere where there is demyelination or any kind of um potential for potassium release, Succi will increase that. And you can get quite profound um potassium release and uh hyperkalemia because of subs with hernia, single dose. So, um that's where it, it becomes an issue. Um It was used a lot in pregnancy um and it was probably the last place that it was used as a routine drug. Um but pregnancy is one of those conditions where you get acquired plasma cholinesterase deficiency. So you get a prolonged action. And so if you get a difficult intubation in a pregnant woman, um Sasia is really quite, it can be very variable in how long it takes to wear for it to wear off. Um So that's the issue with SME in a lot of in the UK and in some of the other countries have primarily been replaced by Rocuronium. OK. Um So ro your own is probably the, the has become the, the uh muscle relaxant of choice for rapid sequence induction, it has a dose dependent onset. So if you give 0.5 0.6 mg per kilogram, you get a uh a uh onset time of three minutes. If you give 1.2 mg per kilogram, which is the, the razes induction dose, you get an onset of time of between 60 seconds to 90 seconds. Um it is uh painful to inject when you inject it. And if they're a little bit light, you will see them move their arm. It does, uh, hurt when you're injecting it. Um, and it lasts about 30 minutes. It is eliminated via uh mostly by hepatic elimination. So you've got to be wary in patients with liver failure. Um uh So it is something to be aware of that you can get prolonged. You, uh uh um it can last a long time. Um You can reverse it using the traditional neostigmine, glycopyrrolate reversal agents. Um But uh for, for pregnancy. So for cases where you want immediate uh rapid um resolution or, you know, reversal of rocuronium, um There is, there is the drug Sugammadex, uh which um, has come off patent in the UK just recently. So it's more generic. Um I don't know what its availability is like and how expensive it is in other parts of the world. But um it is, we, we're reluctant to use it over here because it's because of expense, but it's now that it's become a bit cheaper. We're more, we're, we're more um it's more become more widely available. Um But it is the um the drug of choice when we're trying to reverse somebody is, is the gamma. It's a specific reverse reversal agent which encapsulates the rocuronium. So it can be used in hepatic liver failure. It can be used in um uh to reverse profound um muscle relaxant. So if you induce somebody, you can't find they can't be intubated for one reason or other, you can use the gamma to completely reverse the Roy radium. The other commonly used drug uh muscle relaxant. These are, these are all non depolarizing, muscle relaxants. The other commonly used, one is Atracurium has a dose uh as a dose of 0.5 mg per kilogram, uh onset is three minutes. It can cause histamine release. Uh and you can get cys cis atracurium, which is a um uh so, whereas abnormal atracurium is a, is a blend of different isomers. Cys A is a specific isomer uh I isomer um which is supposed to, in theory cause less histamine release. Um The reason I've mentioned it specifically is it's, it's, it's probably the go to in liver or renal failure because it goes through um Hoffman degradation. So it's not dependent on renal or hepatic elimination and it lasts about 20 minutes before it wears off the others such as vecuronium, pancuronium, pancuronium is used much more in neonates and our neonatal icu um, it has a dose of 1.2 mg per kilogram, uh, onset times 2 to 3 minutes and it, it lasts between 60 90 minutes. It's a much more longer duration. Vecuronium is in between, between rocuronium and pancuronium. They're all similar in, in nature. Um, has a slightly, er, it's more potent as a low lower dose but again, it has a 2 to 3 minute onset time but it can cause bronchospasm hypertension partly due to histamine release and it lasts about 45 minutes. So you can see that there, there is a spectrum of, of, of muscle relaxant you can use. So I've kind of covered this quite briefly, quite quickly because I wanted to talk about um, some of the things that you've asked about, um, as I said, personally, II I don't, I don't, I don't tend to use suxamethonium very often. Um because of the, the, the side effects profile that it has. Um, but we have used it for many years without that many problems. It does, it has a, a higher rate of anaphylaxis than rocuronium. Um, my, my default personally is Rocuronium for any rapid sequences and acu for anything else. Um, prior to, prior to Roy radium gamma day is becoming more popular. You used to give you used to get sushi to, to get them intubated and then give, er, and then make sure they um are recovered. So do some sort of test to check if um the pro the sucks para has worn off before you give the atracurium, if possible. Um particularly in cases where there is a likelihood of, of any kind of plasma cholinesterase deficiencies, any questions. So I'm hoping to do uh at some point, um if they'll have me back um to do a second session, going through opiates and going through uh things like local anesthetics and um some of the uppers and downs that we use. So, uh some of the other kind of postoperative nausea, vomiting drugs. Um and uh uh what else we use? Some, some of the kind of I tras that we use. Um what are the conditions where we use to choose Dione? Uh are the propofol. Um So some people, um so uh propofol has egg protein in it and in, in theory, people are a bit wary of giving propofol to people with egg allergies realistically. Um Most people with egg allergies are allergic to the albumin. There's something in one of the egg proteins that have albumin, whereas the propofol is derived from a different type of egg white protein. See thin, um which is um where, where, where, where you use that? Um I would use thiopentone in an in um in if I could find it. Um And if it was available, my preferred choice for inducing somebody in status epilepticus um because you get clear burst suppression eegs. So that's when I personally that was my main reason for using um thiopentone um uh because of its availability and familiarity. Um The, the reason why um people use profile again, it's familiarity. There's no reason why you would choose, you, you could use, choose either um for R I. Um So the, the standard that people tend to use is an opiate. So most people here use a modified RSI. So we would do a um uh an, an opiate of some sort. So whether it be uh alfentanil fentaNYL SUFentanil depend on what's available. Um And then you give your induction agent. So Propofol or um uh tho would be my, our defaults. Um Apart from in those cases with uh such as uh hypovolemic shock where you might want to use ketamine and then you would use your muscle relaxer of choice. So either sucks or rock. Um We still use cricoid pressure here um As our default again, um we have suction under the pillow. Um uh And then if you're using socks, you wait for the fasciculations before you intubate. Um As I said, the kind of the default for or the, the, the traditional book textbook answer for RSI S RA deductions is tho because it gives you that predictable and you can be quicker with it, you can go, you know, opiate Dipentum, muscle relaxant and you'll be confident that if you're given a 3 to 5 mg dose, they'll go to sleep. So, from an awareness point of view 5.10 is the textbook answer. The problem with um uh the, the um uh Dipentum is that you can either overdo it and under do it. Propofol gives you much smoother, but it's slower because you're titrating to effect you, you tend to kind of give it wake enough sleep and then give your muscle relaxant. So it's a bit slower. Um But for most people, that difference in time is not clinically significant and the, the smoother induction profile means that we prefer to use Propofol. That's why I would use Propofol while Viento. Um If you don't have any benzodiazepines, you can use Ketamine, but you just go when they wake up, the best thing to do is keep them in a, in a quiet darkened room. Um because that tends to be a, a good way of preventing those hallucinations um rather than uh rather than anything else. Um Opiates haven't been shown to be of much benefit. Um uh Really, um I'll talk about local anesthetics at another time because time is limited. I don't, we can go into detail about the different local anesthetics, what you would choose what you put spinals and all that kind of stuff. Um and a separate session because that's the whole big topic. And it's an interesting question is ketamine, traumatic brain injuries. Um So it depends on what your primary, your primary issue is. If your primary issue is a traumatic traumatic brain injury and you're in a, in a, in a low resource place, then you'd probably still go with Ketamine because of it's in your hemody unstable patient because of other injuries. So most of our trauma patients have multiple injuries. They don't tend to have just a traumatic brain injury and providing you can then do all the other things to prevent secondary injuries such as making sure um you get a um you know, good oxygenation, control their CO2 to normal, not, not hypo. Uh You don't want hypoc cardia, you want hypocapnia, you want um no apnea, you're probably better off having a smooth, stable induction and having a slightly increased cerebri buff load than having profound hypotension or hypoxia. So, um if I was in a well resourced area where I've got all the kit that I want, I probably wouldn't use ketamine. But in prehospital care, they use ketamine for a lot of their trauma patients because of the lack of resources and you're better off making sure that they can keep breathing. So, you know, you know, if you have a, a difficult intubation in a an award place, you haven't got all the quit available. Um then you can um do you're probably better off using ketamine, making sure you intubate the patient, they don't get hypoxic, you can ventilate them clearly. That's probably a better way of doing it um Than nothing else in terms of books. Um There are lots of books that are out there. Uh The one I've uh 11 of the ones I've used is training anesthesia, um which is, it covers most of things that uh we cover in the UK. Um It's quite in the modern book, it's much more clinically focused rather than being a lot about facts. Um And it gives you a few bits and pieces. Um, other books that you can use are so that gives you more details. Um Obviously that, that there's, there's the opposite handbook of Anesthesia, uh which is um has got all about the different um different things you have to consider for different types of operations. So, you know whether there's parathyroidectomy, what type of operation you've got, um it gives you the things that you have to be aware of. Um if you're looking for specifically details about drugs, um specifically, if you're doing kind of exam based stuff, boards, things like that, the drugs and anesthetics and intensive care is quite a good book for that. Um So these are quite simple books. They're, they're not, they cover all the drugs you might be, might be have, might have the essentials. Um canu the term used in birds in the early stages. Um So we, we tend to avoid it, you can use it in the very early stages, but after any kind of period of time where um uh you have to be much more careful um because of, of um the potential of, of of release. Now and again, it depends on the anesthesia is quite nuanced. It's not one of those ones where you have to be. Um uh there's no all or nothing. So, um whilst uh it has no benefit, it has benefit in terms of its rapid onset. And if you need a rapid sequence induction because there are other rings in it, including burns, you might want to avoid it or might want to give it. Um But I, I personally wouldn't use it. II, I tend to use other drugs. So I, I will tend to use acu or rocuronium for most of these things. Uh depending on what the other, other issues are. Um Yeah, it also depends on things like, you know, whether they've got carbon monoxide poisoning, if they've got is the airway going to be difficult because of the, the airway burns, things like that. Um If the patient has multiple comorbidities, COPD, heart failure. Uh So it, it depends on the type of heart failure, the degree of heart failure um COPD um in COPD, I wouldn't use anything that causes bronchial constriction. Um So you, you, you know, it depends on the operation as well. So I would go for a very stable onset uh anesthetic. Um So, um first of all, can you avoid G A at all? So can you do some, you know, I have the benefit of having be able to do um regional anesthesia or uh spinal injections for anything lower, lower limb to, to avoid, particularly if they've got COPD. Um, and it's all about risk benefit. So, even if patients are aspirin or clopidogrel, if, um, they have, um, uh, a femoral fracture, I might do a spinal because actually if they've got quite severe COPD, I'd rather them have a, a spinal and, and treat the hip fracture, um, than, than do, um, a general anesthetic heart failure. Um, uh it's, it's, it's much more difficult because it depends if you've got systolic heart failure or heart or diastolic heart failure. Essentially, you want a smooth, stable uh induction, you want to maintain their, um their forward flow. So, BP perfusion, um and often doesn't matter which drug you use, it's how you use it. So, even if I'm using Propofol, which can drop your BP, I'd give very small amounts. And a lot of these patients with heart failure have very slow circulations. So I would give, you know, the whole point of titrating effect is you give it two or three mils, four mils, maybe give it time, see what the effect is. Give a little bit more, give it time, you know, you have to balance the need for an RSI versus um the stability of induction. And that's where it really comes to. If somebody's got bowel obstruction and they're vomiting and they've got heart failure, they're at high risk of aspiration. So I would do big opiates. Lots of opiates, not much anesthetic, whichever you choose, I might put some benzodiazepines if I have them available, um, to, again reduce the amount of, of, um IV induction agent that I would use and then, um, and then keep them to put them to sleep. I've been very, very carefully increase the inhalation agent because I, I don't want that massive increase. Um, and then they get that precipitant BP drop. Um, I often give, um if I, if I notice that their BP is dropping or tailing off on what their normal is, I'd give them some uppers. So phenylephrine me, traMADol, whatever you've got available, I'd give, give that to try and um uh minimize uh that, that, that drop before it happens. Um Some comorbidities have a priory of others. So things like diastolic heart failure is really, is, is, is really hard to manage. Um So uh right sided heart failure can be quite difficult. Um Whereas, you know, mild COPD, um the issue is about extubation. So if you've got, if you've got severe um COPD, you got to mean you might have to wean them for a period of time, it might be harder to extubate them straight off, particularly after a prolonged operation. You might need to need to do some recruitment movement maneuvers to make sure they're oxidated properly. You might need to increase the amount of peak they're giving and whether that's manually, whether that's um uh through some, you know, ventilator. So I've often just, you know, turn them, taken them off the ventilator, um, manually given them a prolonged high medium pressure. So I might put the APR valve at 20 or 30 give them 2030 seconds of, of um, uh a, a continuous pressure to try and open up the airways before putting, uh taking off the, uh, putting back on the ventilator with a slightly higher peak. Because if you've got at Alexis, just increasing the peak itself won't open up anything. It'll keep things open but won't up, open up anything. Whereas if you open things up first, then increase the peak that tends to work a bit better. So it is very difficult to kind of go. There's not one comorbidities, is it the severity of the comorbidities and often the combination of comorbidities that, that, that is the issue. Um, rather than, you know, if somebody's got heart failure and COPD, it depends on which one's more severe as to which one you're gonna take, pay more attention to. And then what anesthetic drugs matter with what matters half life or on set date or both depends on the situation. So for example, if you're doing a rapid induction, then the onset is, is um better. Whereas, um if you are talking about, um uh you know, we, we, you know, muscle relaxant, you short A has two components to, it, doesn't, it, it has how long it how long it lasts. Cause you know, if you've got a 20 minute, a 10 minute procedure, you don't want to give pacu, it's gonna last an hour. Um So it's, it's that combination between, um, the, the most appropriate half life and the most appropriate onset of duration for both induction agents and muscle relaxants. There's no, it's not one matters more. It's, it's putting them into context of what you need them for. I think that's us. I think you had a whole pile of questions there. Didn't you come in and I think I heard that you were gonna do another two talks. Is that right? I didn't want to do another one. I, I, when I, when I started this, I planned to do a whole section and then realized that I probably wouldn't have enough time to cover it and give them it. It's kind of what they're worth. Perfect. Well, we'll take you for another couple of sessions if you're prepared to offer it. So just so, uh, delegates know feedback form will be in your inbox now. And, um, please do. There's a question in there that says about, um, what kind of further information do you want on this topic? Please fill that out. I'll be here, I'll be sending all that off to a as well so that he can see how his feedback was and he can, um, then look to see what to include in his next talk. Ok? And also please fill out the feedback, just show your appreciation as well. You know, a has given his time to us today and he will again and we just wanna, it's one way that we can show our appreciation is by filling out the feedback form for him. Ok. So that's it from us. Um, we have another event come the end of the week as well. If you want to tune in for that one, it's all on A HP, I believe, er, and Gyne and then we have a cardiology event on Saturday as well. So do take a look at those and this event will be on, catch up, er, later on during the week. All right. So that's, um, so we'll say goodbye now and we will all, we will see you again soon. Ok.