Hey Landon here, episode 42. God a little long, but it's fantastic. So we split it into two parts. Part one is going to be about Ketamine dosing, procedural sedation and pain control, and in part two we're going to talk about intubation, behavioral control, the effects on physiology and some of the trend to use this for it. So make sure you listen to both and we know you'll enjoy our first guest speaker ever on the podcast.
Speaker 2:Hi, it's landon. Hey, it's money and we're kind of excited today. We're not in my kitchen of knowledge, different kitchen of knowledge. We are definitely and we have our very, very, very first yes speaker. Yup. Say Hi. Hello. Oh, uh. So we're honored today to have Dr Gary Dull Fado on our podcast as our first ever guest. Gary, why don't you tell us a little bit and we're gonna talk about Ketamine today and tell us why you are interested in ketamine and kind of what your deal is with ketamine. Awesome. We'd be happy to. First of all, thanks very much. Always fun to see you guys. Oh, thank you. Can, I mean, is far and away my most favorite drug, Doug, of choice. Not just recreationally,
Speaker 3:but uh, no, we use ketamine on a daily basis. I don't think there's been a day that's gone by in the past 15 years where I hadn't just kidding me. So we use it for all sorts of things from Analgesia, sedation, agitation, control, you name it. Um, I got an interest in using ketamine really because I became an accidental researcher about 15 years ago where, um, we were looking for different ways of sedating people and we, um, we thought it might be a good idea to start mixing ketamine and fall together and started playing around with that and found it worked really well. And then when I went to look at what literature there was on that subject, I realized there was none. And so that's how I first became a researcher with Ketamine, was actually in the sedation field where we were mixing ketamine and profile together for fall. After that, realized that ketamine is just a really, really interested in dragging. I became more fascinated with different ways of using it and we eventually came to the point where I kind of thought that we're doing sedation pretty well and there was, there was less to gain and the sedation field and Analgesia was something we did really, really poorly, so I thought there was more to gain by focusing on analgesia and so with my experience with ketamine and the poor experience we were having with Analgesia, I thought the two went well together, which has really been the case. So that's where I become really a ketamine researcher, more than eight Kenneth Fall researcher these days. Excellent.
Speaker 2:Like the Ketamine goober. Yeah. In our minds I was once coined as the,
Speaker 4:you are Italian, so I got all this shit be the appropriate thing, but I think if anybody has read anything on ketamine research, you will have seen Dr Gary Autos name and a lot of those research papers and we'll probably put a lot of that on our website so that you can look at those links. Totally. Um, I think we probably have some questions and you probably have a way of getting to all the points that you want to make about ketamine. And so maybe we should start with you talking about doses. I think that that's probably the easiest because I know that right
Speaker 2:where this all came from was we, we came to your presentation that Canadian Association of Emergency Physicians Conference and you just had a way of making the ketamine dosing a reality for me that a light bulb came on and that's when I turned to many and said he has to be on our podcast. And so why don't you tell us about Ketamine dosing and the ranges and in the way that you do so that, uh, because it was really clear for me. Yeah.
Speaker 3:Yeah, that's a great way to start because, because with ketamine it's all about the dose and kill me. And it's really particular that way that it behaves differently depending on the dose you'd pick. And that's really the special thing about ketamine. And so what I always tell people is that when you're going to use ketamine, what you need to have in your mind is a clear idea of what you're trying to achieve because what you're trying to achieve determines the dose that you're going to pick. Knowing the dosing ranges, this is the easy part. The difficult part is for people to be organized about their intent. So for instance, if I walk up to a patient and I want to, I just wanted to provide some analgesia than I know I'm going to pick a certain dose of ketamine, which you will to be the low dose. Whereas if I walk up to a person and say, I want this person completely unconscious so I can reduce their fracture, I know that I'm going to pick a high dose of ketamine. And so. So those things is a great structure to start on. So I guess starting from the bottom up, ketamine isn't analgesic that has been well established and it's analgesic in a very, very low doses. When you look at human studies doses as low as zero point one milligrams per kilogram. There are human studies on that dose and no question that it does provide analgesia. When you see people using it in the Ed to the usual analgesia range is anywhere from zero point one to zero point five milligrams per kilogram. When you get above zero point five, that's when people start to become disconnected from reality and that's where Kevin even gets its name as a. it's called a dissociative anesthetic. Basically you're disconnecting the brain from people's external reality and when you get up to half a milligram per kilogram, that's when that disconnection really starts to manifest itself. So low dose under point five, then high dose is considered above one point zero, so that's when people start to become fully disconnected. And so when you're using ketamine as a general anesthetic and it is a general anesthetic in high doses, you're talking about doses of one milligram per kilogram and above. So that's considered high dose ketamine. So low dose under point five, high dose up over one point zero or the two zones where you really want to operate. So there's a, there's a middle ground there,
Speaker 2:five to one, and I think you have an opinion on. I've intentionally left the middle ground for last
Speaker 3:because the middle zone is the minefield. That's where you don't want to be stepping. This is where ketamine gets its bad reputation because people are partially disconnected, you know, partially connected, partially disconnected, and you really have very altered perceptions of reality. Now lots of times it's quite enjoyable. In fact, that's, that's the party drug reps, the party drugs zone. And so, so a lot like no ketamine's parent drug which is PCP or angel dust. So when people had their acid trips in the sixties, well, do people still have asked?
Speaker 2:I don't think. I don't think so because she was alive then. Not at all at all. The raves nursing them all back to back in the sixties with her lanterns. You work. Did you go to school or Jimi Hendrix? Yes, I did. Actually any many knows Florida. And uh, that was well in our podcast, that acid choosing ECP, just so you know, I'm sitting between them. Exactly.
Speaker 3:So, but anyway, the middle zone, that's where people can have a good trip or a bad trip and most people to be honest actually do have a good trip. That's why it's such a popular drug. But the people who have a bad trip, the trips are so bad that everyone remembers it for the rest of their lives. And then this is where the stories of these horrible trips with Kenny come because these really horrible things, although they're relatively rare, there are so profound that everyone in the room, everyone in the building, sometimes everyone within you know, 500 yards, you know, here's a book, this big reaction and that's where can we get this fearsome reputation. So it's a bit overblown in terms of, you know, statistically the likelihood of it to happen. But if it does happen to you, you will never forget it. So it's nice to avoid it and there's an end, there's no utility to begin to being in the middle ground because we're either providing analgesia in the low zone or we want the person fully sedated in high zone.
Speaker 4:Can I ask you a question because I'm sure some of the nurses will want to know that is there in that middle zone because it is a party drug, is there an addictive piece of it that people become. I guess it's with like anything that you're addicted to. If you have an addictive personality that happens, then I likelihood that you'll continue to do that. So. So Kenny means
Speaker 3:it doesn't cause addiction in the same way. For instance an opiate, but like you don't get a withdrawal syndrome if you stopped taking ketamine, but other than the psychological addiction change to that feeling then it. So it's not truly addictive physiologically though I suppose it would be the experience would be addictive mentally. Is that where that middle zone cleared, that emergent reaction? I think everybody's worried about happens. Is it? Exactly. Yeah. So, so here's where you have to be careful about your dosing. So if you're providing analgesia, like I mentioned before, the analgesics zone is below zero point five milligrams per kilogram. What I recommend to people is if you're using it for Analgesia, you actually want to go lower than that because people, because everyone else, everyone's an individual and some people will get into that middle zone at point five, milligrams per kilogram. So others as the years have gone by and people become more experienced with using ketamine for Analgesia, we found that cutting the dose down, you still get a solid analgesic effect and you minimize those adverse effects, you know, the, the partial dissociation. So I actually have recommended starting dose of point to two people commenting. You commonly used point three, um, and there's even been studies comparing point three to two lesser doses, like point one, point two and you get a slightly better analgesic effect, but still pretty similar. But the number of adverse effects are much, much less. So I think the magic, the magic dose for Analgesia, I think, I think the most logical starting dose is point two because that's where you're going to get a good solid analgesic effect. And you can minimize the amount of adverse effects. You're still get adverse effects, they're just not a big deal. So when we use ketamine and we use it intranasally as well as intravenously, much easier, everyone, everyone about 25 percent of people will get a noticeable adverse effect. You know that 25 percent is booked the same as you get when you use morphine. The adverse effect, right? So I tell people that adverse effects are not any more common than navy if you use opiates, it's just that they're different. And that's where people seem to have an uncomfortableness with ketamine. No. If you give someone an opiate and they throw up because Oh, that's just the opiate and we're all comfortable with that because we grew up with giving opiates and everyone knows what to do and no one gets bothered by it, but it gives someone a dose of ketamine, they get dizzy, and then all of a sudden the EU, it's ketamine. Oh my God. It's a terrible drug and I think it's just a familiarity thing. So I think as the years go by, we're going to become more and more used to decide effects that happened with ketamine. They're just different than what we see with opiates. When you use a low dose is the number one thing is people get this, what they call a feeling of unreality or they'll say dizzy. They'll just feel weird and the effect, and I've actually had low those ketamine for analgesia due to a. A relatively recent orthopedic clinical
Speaker 2:reason don't lead to more research. That's it. That's a different heroic survival story. You have different pot, different podcast,
Speaker 3:so the effect is much like you wouldn't have if you went for a bike ride, came home, sat on your back, duck back deck and drank half a beer where I describe it to people as saying, you know, I might, I'm not going to jump behind the wheel of my car because I'm feeling just a little tipsy, but I'm feeling together enough that I wouldn't be bothered to sign checks. So and that's the experience that people have with that low dose of Ketamine. Something's going on here. I'm feeling dizzy last about 20 minutes goes away. You do not get into any of these weird hallucinations and flashbacks and things that the stories that people hear about and the other bad effects said people fear about ketamine, like no laryngeal spasm and hypersalivation the things that are the subject of horror stories never happens in low dose, just can't happen. So it just, if I can jump in. So when you say low dose and you're talking to point two milligrams per kilogram, that's ib bullis excellent point. And that is right. That is the, the dose when we're talking intra nasal administration, because instruction is about 50 percent. Just double everything. So okay. So if I gave point four milligrams per kilogram of ketamine intranasally, I'd get about the same effect as if I gave point two milligrams ivy. Okay. And if I had someone say with a femur fracture and you're saying this lasts for about 20 minutes and like giving this every 20 minutes or is it sort of, this goes away. And then the pain control is for a longer period. Exactly. Right. And this is, um, this actually relates to my personal
Speaker 2:be the denture, which, which was a fractured femur actually. That's why I picked that.
Speaker 3:Yeah, it was a fever, but it was very, very proximal on the people. Some people might call it a hip, but that,
Speaker 2:that's enough to be a hip fracture. Said that before different street, a Femur and hip fracture is your age?
Speaker 3:No. So, so the side effects last about 20 minutes and then, but the analgesic effect less two to three hours. Okay. Wow. And, and this actually relates to even my personal experience with intranasal ketamine where I had an intranasal ketamine alone with nothing else and had very solid analgesia while I was waiting for surgery for, for two to three hours before I needed anything else. Okay. Although the side effects, they go away in 20 minutes of reliable. That's great to know because I know we, we, when we use it in higher doses, it's Kinda, you're asleep for 15 to 20 minutes, then you wake up. It's good to know that that pain control lasts more than just that 20 minutes. And that's part of the reason we started using it.
Speaker 2:It there's was a number of reasons we use ketamine as usual with our podcast. The garbage truck is kind of, no matter where we go in this world is following, do our podcast. The garbage truck always comes by. Well over time would always. You always do this garbage day and if we're here at different days or even in a different city. Exactly. Only the philosophy to me is what you're saying is we should start low and go slow. If you're using a parental he's. Yes. Yes. So start low, go slow. And because it's milligrams per kilogram, it shouldn't make any difference if it's peeds or adult. That is completely correct. Okay. That's helpful. I think for us, the only difference between pediatrics and adults is that the pediatric population is much more resistant to the adverse effects. The garbage truck will be gone in a moment. Now we're going to hear the beeping as turns around at the end of the road. I don't think they ever be. No. Okay. Is this word make a joke about this is actually monique's other vehicle? Yes. Very much, yeah. Yeah. So when you're using it pediatrics, your freedom from adverse effects is even greater because the pediatric brain for reasons I'm not sure of, is more resistant to the adverse effects. Oh Wow. Yeah. So Ketamine is always more of a concern in adults. Okay, that's interesting. I didn't know that. That's low dose. Low dose. So let's talk high dose, High Dose Ketamine. I love high dose. High dose with no because it's not true. I haven't remembered anyway. So it wouldn't be for high dose. We were saying we're for general anesthetic, so the difference between conscious sedation and using it as an intubation. Maybe we just talk about those two things. Sure, yeah. Although nobody ever calls it scares me. That's being what she tells me. Oh that's old terminology. It is alternative for sedation. Yeah. So I usually say let's do, I will not do conscious sedation, but I'm happy to do some unconscious sedation. Fine, fine, fine. So. But no. So Ketamine in high dose is a very useful drug when you want to achieve complete control of your patient very quickly and that's, that's where ketamine might actually be the best drug in existence, I think to achieve that because nothing can get complete control of your patient quite as quickly and keep them breathing at the same time. So that's a. that's a big high note they're on this drug is no matter what we're doing, they should still be breathing. And if they stopped breathing, it's not the ketamine. Let's stop the breathing. It's almost never,
Speaker 3:almost never going to be. There's a little star that sentence here about at some point there's always an asterisk to everything. So Ketamine, if you give a high dose of ketamine intravenous very quickly, it's well known that people can stop breathing transiently. Okay? But no one ever has to do anything about it. They'll just start again. So, so those people that tell you, I gave a kid, I saw ketamine being given and they stopped breathing. Well sure it can happen, but the academy itself only caused that transiently and nothing needs to be done about it. It's usually has more to do with the population you're dealing with. Usually the reason we're using high dose ketamine is you could. You've got a sick, unstable patient in front of you and bad things just happen to stick on unstable people and giving ketamine doesn't change that. No bad things still happen, right? So, but to backtrack, just slightly so achieving full control. So Ketamine is great for it because you can give it ivy, you can give it. I am and both are extremely rapid ivy, you'll get complete control in under a minute. Whereas I am, you can get complete control in under five minutes and there's really no drug will support the blood pressure. Like ketamine does keep people breathing like kilometers and achieve rapid control that quickly. I don't think another drug exists and that's why I think ketamine is tailor made for, for that kind of use. So we use it pretty commonly used. You mentioned sedation. So for sedation we'll use, we can use ketamine by itself and that's very, very effective because you get complete analgesia, you get complete amnesia. Um, you get complete control of your patient and you can do anything to them. In fact, it's the most used anesthetic worldwide when you look strictly by numbers in, in, in austere environments. Third World countries, they have no monitors, they have no other drugs, they don't even have sat probes and they do general surgery under ketamine alone routinely. And there's, there's cases like tens of thousands of cases. The safety profile is remarkable with no monitors were of course very blessed with all our monitoring capabilities and things like that. So, so if we're doing a procedural sedation, it's small potatoes and you can do anything with ketamine alone. Now, I almost never use ketamine by itself for sedation for one reason only. And that is it lasts too long for what I want. Sedation analyzed by mixing it with proper fall, we can get the same type of total control, keep them breathing, and we have a duration of 10 minutes as opposed to a duration of 45 to 60 minutes. And that's way better for, you know, departmental flow. So that's really the story. You're giving less of a dose then because you're mixing it with profile that the profile makes it not last as long as you're giving a lesser dose, you're giving less. So, and this is something we actually proved with when we did our randomized double blind trial, is you do achieve the exact same sedation depth using half doses of propofol ketamine combined together. So the two drugs really are synergistic. So, and this is an argument I had with so many salacious who refused to believe that you could use sub sub anesthetic doses of two drugs were completely different mechanisms mixed together and achieve the same depth of sedation and we have. We basically proved that you can. So we're using half a dose of profile that we would normally use compared to what if we were using propofol alone, half the dose of ketamine that we would normally used. Comparative who ketamine alone, mix them together in the same syringe. You get the exact same depth of sedation, much shorter recovery time. And and for me, that's. That's one of the, one of the two big advantages of using Kenna. Kenna fall over ketamine, shorter recovery time. The other big advantage is that profile being a good sedative, it actually naturally counterbalances those adverse effects that people don't like giving half dose. Ketamine, you're almost in that. We never want to be here zone dosing anymore. Right? You can get there. Yes, but the pro profile will tfr, so if you use ketamine and you're in that middle zone accidentally, someone gets an adverse reaction, what do you do? You just give them a sedative and then you wait it out. Kevin levels drop and everything's fine. So purple Paul is a sedative, so by using protocol together, we found that the those, that adverse event rate is cut down by an order of magnitude like only a 10th of the people that would have had an adverse reaction do when you use the protocol along with the Ketamine. The other big advantages that probably fall has actually been shown to be a really strong antiemetic and one of the adverse effects people don't like about ketamine has that feel of nausea and vomiting. It's one of the things that detract from its use. And guess what? When you use propofol, ketamine, the uh, the nausea, vomiting rate goes way, way down. In fact, the effect has been shown to be equivalent to the detective Gibson get with our dance trunk. So if you're using doing a kidman, sedation and child and especially in an adult and you want to lessen the chance of analysis event, not having them vomit, just give them a little protocol because you're giving half doses of profile defined the hypotension or the blood pressure impact is less 100 percent. That is, that has also been well established physiologically. We know that when we, when we give kid a fall, like ketamine profile and you can get a single strategy or separate syringe. Quite honestly, I use both, I think. I think they work equally well. It just depends how you like to give it, but using ketamine profile together, blood pressures will tend to go up without a question. Now, does that matter is where the debate is and in the gym, and that's a problem with some lot of the. When we look at this is when you look at the general population, like everyone we sedate blood pressures go up a bit, compared that to portfolio alone. We don't see much of a difference because we're doing. We're generous today. Eating pretty healthy people like they don't have a lot of baseline morbidity and the ones that do it, there's not many of them, and so if I gave proper fall to you, your blood pressure will go down, but it doesn't matter because then it'll just come back up again. Right? But if I was to say to date someone really old, I'm not looking at.
Speaker 2:No, of course not looking at if you've got pneumonia and needed to be intubated, don't let them just give me proper fall along. I'm sensing that might not be. No, but
Speaker 3:seriously, I'm seeing an older person with a bad heart. This is where using propofol alone has been known to really get you in the weeds like blood pressure team crash when we're talking code status crash and it can be very, very difficult to get them back. This is where using ketamine alone with the portfolio is a huge advantage because that blood pressure support will keep them from crashing. I'll keep you out of the weeds, so no one's done that. You know, no one's ever done a double blind randomized study randomized to these little people, little old ladies with that heart rate. We're going to sign this
Speaker 2:incident form. We're going to see if we can kill you. So no, I
Speaker 3:don't ever do that definitive study, but there are large series of using it in older adults for um, for sedation and all sorts of other things. And you find that it's perfectly safe.
Speaker 4:Okay. I think one of the things that I probably have a personal biased against is using proper fall alone because it doesn't have an analgesic effect. It also, if you're using a procedural sedation for reducing something that's broken, I find it really difficult because you're catching once they come out of the proper file, they're in so much pain that I find using both anecdotally, for me, caring for the patient is so much more humane than proper follow along. I don't know,
Speaker 2:you've touched on a subject near and dear to my heart. Excellent. And that wasn't even scripted. Yes, I would agree with you completely.
Speaker 3:Yeah. But then I will also tell you, I'm not sure if it's true and I'll tell you why this is. This is something that's of great interest to me. So when I started using propofol sedation drug, I really felt bad because propofol is not an analgesic and yet we're doing something painful to people. And so I said to myself, if I'm going to do something painful, I want to give them a painkiller because that makes me feel better. I feel like I'm doing the right thing. And so for years we added propafol and Fenton altogether, right? Can we go on the opiate because that made me feel better. There was those that argued, you know, the person doesn't remember happened to them and they wake up. Does that, does the pain matter if they don't remember it? That's a very interesting subject and it gets really quite complex because we know it does matter when you do surgery. There's this thing called these surgical stress response. Um, it's well known that if you do general surgery on someone who's completely at the deep in the deepest state of anesthesia, if you do not provide an analgesic, even though they're completely unaware and completely unresponsive, they will do worse later. They have more hospital days, more pain, and even a higher mortality. So that is true. And so people said that's what happens during surgery, but this, that's still true in the short procedures that we do in the emerge department. To me it was logical and so I thought, well it probably does matter and so that's why I was providing analgesia. And then someone actually tried to look at that question in emergency department sedation guy billion with Jim Minor, who is one of the WHO's who of sedation research. He did a study where he gave people just profile and did orthopedic procedure and then he gave other people propafol along with an opiate. And as a measure of stress, he measured cortisol levels, like cortisol levels every, you know, every few minutes they did blood samples measured, essentially know what kind of adrenaline responses is patient having. And they found that there was really no difference in the people that they gave the opiate to comparing really, um, when, when the actual doing the procedure. So adding an opiate did not seem to decrease the amount of stress that actually let me reverse that. Not giving an opiate didn't decrease the amount of stress the patient felt during that really brief procedure. The only time that patients exhibited more stress was when they became hypoxic. Our really, which is very interesting because now I'm, I've decided I want to be a good person and I want to give a painkiller and opiate to this person I'm giving propofol to. So I've just doubled down on my respiratory depressed, on the hypoxia. So by making myself feel better, I've increased the chance that my patient is going to become hypoxic. I'm actually in the process of making myself feel good about myself. I'm actually putting the person at higher risk. Oh, interesting. And that just drove me crazy. It drove me crazy now. And, and then I don't know what to do now. I don't know what to do. I know now it's the future of his research career, but this is where for me, the answer came to using ketamine with the profile, so now I can provide an analgesic without doubling down on that respiratory depression. So for me this no one really knows the answer to the question. Doesn't analgesic matter during the time of the procedure? No one sure knows the answer to that question. So. So I think if I can still make myself feel better because it is logical, I no one knows the answer one way or the other so it's not wrong, but we don't know if it's right, but if I give them an analgesic using ketamine, I know I can provide that analgesia without causing an increase in respiratory depression. Right? And so we can achieve, I think the best of both worlds because it is true that after our things we do that after the procedure. It's painful. It's very painful. The two classic procedures are would be a fracture reduction and incision and drainage where we're after you're done, this person might have as much or maybe even more pain than when you started. This is where I think ketamine is perfect. Yeah, I agree. Because it's going to carry through after procedure and decrease the level of pain, let's say for a cardioversion where the pain is instant and Conrad away. Exactly. It wouldn't be that neat and this is a circumstance where even though I've gone back to using appropriate protocol, but cardioversions the only one because it's so brief, they really don't have pain afterwards and I think that's perfectly logical because you know, really for department flow. So yeah,
Speaker 4:and I think that's something. But I think that that's something you an island and they've talked a lot about with nurses is understanding the why and the purpose of what you're doing really helps to advocate the best for your patient and to also speak to your physician in a knowledgeable way about saying, well, this might hurt a lot. Do you think that just giving proper fall for this fracture reduction. I'm wondering if we could give some ketamine as well because once you leave this patient is going to be in a lot of pain. So having that real professional discussion at the bedside about the choices of the analgesic sedation that you use and the purpose for why you're doing it and I think coming in with knowledge and having that discussion is so important.
Speaker 3:Yeah. Yeah. I mean 30 seconds before the procedures from the start might not be the best time.
Speaker 4:No. All this pre free preemptive Dr Dr Levine questions right before the thing. Yeah. But I do think it is something that if we're having planning, right, like we always planned for it. So what's the best thing to get everybody at the bedside and that let's talk about this and all of those kinds of things. Right?
Speaker 3:But, but any doctor I know and respect would be very open to, to, to having a discussion then. Absolutely. And this is where having some resources or you know, at your fingertips or online, which is really great because people love reading about that stuff and you know, even if they have to think about it right at that moment, you plant a seed of something that someone's going to think about later. You bring that up for departmental discussion. This is, this is how change happens and can happen positively that way. Yeah, absolutely. It's not a. it's not a questioning. It's more of a more of a discussion.
Speaker 4:Yeah. Professional dialogue. Yeah, exactly. Exactly. It's not imagined that professional dialogue has bedside. There's no egos at the bedside to say, hey folks, this is the end of part one. Make sure you listen to part two,
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