The Ketamine Spectrum: From Pain to PSA with Sergey Motov & Ryan Marino

Jason Hine: Hello everybody, and welcome to the SimKit podcast. I am happy to be joined today, not by one, but two special guests. They’re going to offer insight on a topic that I really just think needs more than one perspective to cover it, to talk about it. The use of ketamine in the emergency department. First, I want to introduce you to Sergey Motov. Sergey and I go way back actually I think that one of the first times I met or was introduced to Sergey. I was asking him to come talk at my residency regional conference many, many years ago. And Sergey is an expert in pain management in the emergency department, he’s been researching and publishing on that for years, possibly decades? Sergey But recently, it kind of had a career change for you. It’s taking a little bit of a shift in focus. Sergey say hello to our listeners and tell us a little bit about what you’ve been up to lately.

Sergey Motov: Well, hello, dear listeners, it is a great to be with you Jason again. And you’re right. It’s been I’d say decade of moons that we’ve known each other and I’m honored to be here today with you and to talk about topic that is very dear to me. Ketamine in the emergency department. And as you mentioned earlier, my passion for the past 15 years has been perfecting effective and safe analogic practices in the Emergency Department, but over the past, I’d say seven years, I’ve been primarily focusing on ketamine analgesia.

Jason Hine: Fantastic. So a great person to have involved in this conversation today and we’re certainly going to talk about ketamine and its use in pain. We’re also going to be talking about the full spectrum of its use, and has many proposed uses and really to cover that breadth I felt like I would like, or needed to experts. So I called upon our friendly ED toxicologist addiction medicine specialist Ryan, Morino Ryan. Thank you for joining us today and tell the listeners a little bit about yourself.

Ryan Marino: Yeah, thanks for having me Jason good, good to be here with you. In Sergey. I am an emergency physician and toxicologist and addiction Doc in Cleveland. Ohio. I am a big fan of ketamine in multiple indications and always happy to talk about dosing of medications receptors, all of that, nerdy toxicology stuff.

Jason Hine: Excellent. We want you to get as nerdy as you so choose in this podcast about ketamine, or in general. But yeah, let’s sort of start and go through the spectrum if we can. And in the show notes, we will have sort of information about the dosing, the dosing ranges, and this spectrum of ketamine use and it’s what affects it has on a patient as you get to higher and higher doses. So as we mentioned in the beginning, we’re going to start kind of in the pain realm. In the emergency department we sort of treat pain, I’m sorry. okay, in the emergency department, I see myself and many others kind of having this line in the sand that we create artificially, We give acetaminophen, maybe we give our favorite NSAID, we’ll toss that out like candy. I feel like, sometimes it should just be in the water or the ginger ale that we’re giving patients, right? But when they need something more, then we really start to think sort of put on you know move from that type 1 to type 2 thinking about how we should treat this patient’s pain. Typically folks are thinking about opioids, first at this point, would be my argument, my question for you guys and on Sergey, I’m going to let you lead a little bit I think is, when is ketamine the right choice for pain control in the emergency department?

Sergey Motov: Terrific questions, You know, to make it very simple. And you because myself, I’m probably Ryan with our passion for ketamine. Ketamine is always a right choice, when it comes to analgesia, but, you know, versatility and uniqueness of ketamine in which can be given as an adjunct. To pretty much anything we use. To acetaminophen to end sets to opioids to nerve blocks. You name it. We use it or it can be used as a single entity. So it’s easier for me to say, when I probably would not be using ketamine. And frankly, only one thing pops in mine, is that if patient may have a true allergy to it. Which, after 20 years of practice medicine, I’m still yet to see a patient, with true allergy to get. I mean, in me personally, I’m very coggins of the fact, they do not really use care. I mean, and pregnant patients presenting with a good painful conditions, other ended that if patients presentation, warrant a variety of analgesics and you want to use an adjunct to it, ketamine is a way to do it.

Jason Hine: Fantastic. Simple answer if they don’t have an allergy and they’re not pregnant and you want to augment your sort of standard fare. Analgesics ketamine is an option in your mind Sergey. Ryan, what about you?

Ryan Marino: Yeah. I mean I would defer to Sergey, he really is the expert on this topic, but I agree with what he said. I mean, I think pain is such a spectrum. The person who comes in with a sprained ankle is very different than the person who comes in with a gunshot to the chest. But there is, it’s just such a broad spectrum and the fact that everyone responds differently to the interventions that we use. I think that we oftentimes think of certain things as being too extreme or something don’t work, and it really is kind of just striking that balance where we can give people, maybe they need a couple different things. Maybe we need to escalate, but ketamine is a great option and it shouldn’t really be limited in the emergency department, just because of its really nice pharmacologic profile that works well in kind of the acute care setting like that.

Jason Hine: And so with those ideas in mind, let me push you guys a little further because you, the general settlement is that it can be used really on anyone so long as they don’t have true contraindications. Coming back to you. Sergey what sort of patient characteristics, make ketamine the ideal analgesic for a patient.

Sergey Motov: If we discount what we’ve talked about, obviously allergy and being pregnant in another option is when somebody is a dire strait situation have traumatic hemorrhagic shock. Obviously in pain, but resuscitation takes over you may properly postpone or avoid academy altogether. But in a practical way of saying this…

Jason Hine: Sure.

Sergey Motov: I’ve seen the situations. When patients in front of you because now we’re focusing on patients, specific pain syndrome Target approach to managing their painful syndrome. If you believe that patients, let’s say, opioids, may not be beneficial the risk of having adverse effect outweigh. The benefit of giving is analgesia. Then I have contradication to opioids. Same with nonsteroidal inflammatory medication, a variety of reasons. That’s what ketamine comes into the play. And once again, there’s already emphasize and it’s something that Ryan said, You know, it’s a part of the armamentarium as not, a cure upon a sea for every painful syndrome. But to have this drug this modality available to you. And once again in situation with other analgesic, may be contraindicated or you expect, they will be detrimental to patients well being… Stick together.

Jason Hine: I like that answer. I think that’s a simpler answer that’s more specific. It’s kind of bringing us down the funnel. So if you have Your sort of normal armamentarium. Where an NSAID and acetaminophen and opioid is either contraindicated, not ideal or needs to be augmented, then you would move toward ketamine. Ryan, how about you, What would you answer in terms of like what patient characteristics might make ketamine the right choice?

Ryan Marino: So, I mean, I think there’s a lot of different things that come into play here. Certainly, some of the benefits of ketamine are that it has kind of a very short duration of action and washes out of the system very quickly. So if you need it for a procedure and you think someone could potentially go home from the emergency department, that’s a nice specific situation, other situations where maybe airway is a concern, ketamine doesn’t have the same kind of risks that we worry about on the airway for the most part blood pressure, Sergey mentioned hemorrhagic shock. I mean, I think patients experiencing significant trauma who need imaging and are in too much pain to go over for imaging can benefit from ketamine. And then, in my line of work, I especially see it in patients who are either in recovery from opioids, or trying to avoid opioids, because they’ve had issues with substance use and and don’t want to put themselves at risk. Those are kind of all very specific situations and I think overall, as Sergey said before it really is, there’s no no patient who can be excluded other than like an allergy or a pregnant patient that it comes down to kind of at the end of the day in my mind, just provider familiarity. And so I think it’s underutilized because people are not as familiar or comfortable using it and I think this is a direction that we’re going to be moving more and more towards if not already.

Jason Hine: Okay perfect. I like that idea as well. And I actually kind of want to get a little bit more into what you’re saying there Ryan. I feel like a lot of times the… Ketamine comes into the conversation when we are thinking about or want to avoid opioids. And that characteristics to it. Sometimes actually makes it challenging as well with specific patient populations and I kind of have two in my mind that happened routinely: you know elderly patient has you know rib fractures or has other traumatic injury. We often want to avoid opioids because we have concerns about the adverse effects of these opioids in the elderly or debilitated, but no one really wants it dissociated or high Grandma running around the emergency department in the same vein Ryan, you mentioned, You know, opioid use disorder where there’s obviously a desire or thought at least avoid opioids, but we do find that, you know, concurrent psychosocial or psychiatric disorders, kind of run hand in hand with opioid use disorders. So how do you balance these kind of competing interests?

Ryan Marino: I think I mean it comes down to just kind of the individual situation and I know that’s kind of a cop-out answer, but pain management is really more of like a bespoke patient-centered thing and so it is like we throw acetaminophen and NSAIDs at everybody like you said and it’s not even necessarily those don’t work, it’s just that sometimes they’re not sufficient, they’re not enough, they’re not the right thing for everybody and so the same goes for ketamine. So I think In terms of like the the older patient that you don’t want to necessarily be delirious, we have a lot of risks as well with opioids and things like muscle relaxers, causing that as well. And then in terms of like the psychiatric people with PTSD, who can have kind of worst experiences from ketamine. I mean, there’s ways to get around that with midazolam pre-medication, those kind of things, but certainly always something that people should be cognizant of or at least keep in mind.

Jason Hine: So that’s that’s some good information. And I’ll ask you a little bit more about the details of, you know, augmenting that with other other agents. Sergey, how would you sort of balance those competing interests and I wonder a little bit too if we can start talking about, if you’re going to be using ketamine for analgesia, how do you start considering dosing and coming back to later to what Ryan mentioned? Is there any way to augment the use of this medication to avoid any of its side effects that you might experience?

Sergey Motov: Sure. You know, when it comes to analgesia, I’m trying to be simple as myself. I’m trying to simplify approach and when it comes to ketamine particularly or any other analgesics. I usually tell my fellow colleagues and my residents, I work with, you need to know, three things, You need to know the drug. You need to know the patient, and you need to know Drug drug interactions. The brain continuum of ketamine and obviously what Ryan’s already covered it all together gives you this unique perspective based on the dose because remember the difference between dose and poison is how much you give it. Right? So…

Jason Hine: Mmm.

Sergey Motov: If you’re going to go to the lower spectrum of it, that’s we’re focusing on analgesia. So the range of 0.1 2.3 makes per kilo, giving parentally primarily intravenously or subcutaneously, This is the spectrum that in general, for the most part based on evidence, and we noticed for over, I know how many years would not give you dissociation would probably not you turn into the, you know, semi-dissociated state, will not affect your cardiorespiratory system. And the worst case, What could happen is, it will cause some psycho perceptual adverse effect, which are bothersome and people don’t like them, such as feeling unrealty and dizziness. So, to offset this, which is the most common thing. Is there three things we can do number one pre-ketamine coaching. It was very, very big on me. You tell the patient, the medication may help. The medication has a unique adverse effect that will make you feel like you a quick sand you have out of body experience. And what I tell patients “I’m gonna be by your bedside. And this is transient and within 5, to 10 minutes, it will leave you” and it usually helps greatly second, do not use academy via intravenous push those. If you use intravenous route rather you shorten fusion my own shop, do the study, when we compare interviews push those two short infusion or 15 minutes, if we’re able to reduce those rates of cycle, perceptual adverse effect by 40% without sacrificing efficacy. so don’t push ketamine, I mean, for pain control, use it as a short infusion of 15 to 20 minutes. Lastly, Use lower dose, start with the lower spectrum at 0.15 mg per kilo intravenously given over 15 to 20 minutes, One trial came out in 2021 that compared 1.5 mgs per kilo to 0.3 mgs per kilo. Showed no different for the short term pain. Really, with respect to pain control and slightly slightly, better side, effect profile. So here we go. Should you choose intravenous route: Do the pre-kariman coaching, use short infusion and you can start with the lower spectrum of it does because you can always give more. It’s very hard to take less after a given more.

Jason Hine: I love it. Three usable pearls pre-ketamine coaching. Don’t push it. Give it over 15 minutes and start low. Ryan anything to add or any additional perspectives on that little bit of pearls that Sergey dropped right there?

Ryan Marino: I think those are really useful and I mean the point about not pushing it fast, if you are using any sort of dose that’s more than these low pain does that’s also beneficial as well because the complications that we tend to think of from ketamine, usually are associated with the fast IV push more than any sort of other administration. And this is something that we tend to overlook I think in the emergency department in a lot of cases for a lot of other meds but you can add this to, I don’t know a 250cc, 500cc bag and run it in or just set up the pump and and run it in over 15, 30 minutes. And so those are always options as well.

Jason Hine: Okay perfect. Yeah, I’ve actually in the past put it just to like the 50 bag. You think that? I guess it depends on the IV patency and how quickly things are flowing, but you’re putting it in a little bit more volume to get yourself to that 15 or 20 minute mark?

Sergey Motov: I do 100ML. I personally use 100 ML piggyback

Ryan Marino: Yeah. No, I would defer to Sergey on that. A 100 ML sounds good, and I mean if you have a pump, you can always set it up to do whatever. Whatever kind of infusion rate you want anyway.

Jason Hine: Okay, so perfect. So I would think of that you know similar to some of our medications that you know, can have that acathia side effect. So I use a lot of metoclopromidein my department for nausea. Vomiting headache and I often ask that the nurse put it in a bag, you know, if the patients already receiving IV fluids I’ll put it to that as a piggyback or have it infused slowly to avoid the akathisia. You’re sort of stating that ketamine and it’s psychoperceptual effects or side efects, can be avoided by this slower infusionary is that right?

Sergey Motov: Well, yeah, they can be reduced-  in  fully avoided? it happens. But my majority of patients will experience some sort of degree of the psychoperceptual adverse effect, but yeah, the longer you pull, or do the infusion 15, 20, eEven up to 30 minutes. It’s better for the patient and again, analgesic efficacy would not be sacrificed but, you know, patients comfort and overall, well-being, and satisfaction. Now, paramore when it comes to pain management,

Ryan Marino: Yeah, I think the metoclopromide comparison is good because though that is really how I see them and for ketamine too. I mean if you’re using getting to higher doses, which maybe I’m jumping ahead here, but we worry about kind of the risk of apnea associated with like a rapid push of a higher dose, you can always just infuse it slower.

Jason Hine: Okay perfect and I guess let’s jump a little bit to sort of some of your augmenting medications as well. So for a metoclopromide, sometimes people talk about diphenhydramine for avoidance of some of that academia the slow push Ryan. You’re mentioning some other ways to avoid some of the side effects of ketamine with other agents that you might use. Tell us a little bit more about that.

Ryan Marino: So if I’m using a higher dose, and again, I would love to hear what Sergey’s input is as well. All right, because he knows a lot more about this than me. But if I’m using a higher dose, I mean, the most frequent side effects. I’m seeing are kind of the psychological ones and then gastrointestinal particularly nausea and vomiting. So I almost always will pre-medicate someone with ondansetron or some sort of antietametic but very often if I’m using more than kind of the low pain. Dose will also give midazolam. Or in rare circumstances another benzo, but usually midazoleam as a pre-medication as well.

Sergey Motov: So I wholeheartedly with Ryan and once again, you know, on rare occasions, I resorted to antiemetics and I primarily use Untron as well. Even you too, a view to use benzodiazepines only. Because if I feel patient is having sort of this cycle perceptual out of body experience. You can always load infusion evidence, 30 40, 50 seconds, everything sort of goes away because once again, just to reiterate those other effective of ketamine they are rate in those dependent. Occasionally and small body literature actually supporting the use of using haloperidol, which in theory sort of extends on largest therapeutic window of ketamine towards reducing the incidence of the pyschoperceptual adverse effect on top of working as a anti-emetic. But, you know, you just want to balance the potential for extrapyramidal, adverse effect versus psycho, perceptual ad respect related to ketamine, but these are sort of the options when it comes to pay management using ketamine

Jason Hine: Yeah so tell us a little bit more about that. Are you doing a IV push of your how paradol and and or are you doing it as an infusion? And what’s your dosing?

Sergey Motov: So it’s same thing, it’s a short infusion and those between 2.5 to 5. If I believe primarily I use this mostly for patient with accessoration for any painful conditions and occasionally, you know, particular entity patient with a hyper cannabis and just hyperemesis syndrome, presentation with interactable, nausea and severe abdominal pain. I think haloperidol ketamine combination…

Jason Hine: Sure.

Sergey Motov: It kind of works wonders. You know, you cover all the receptors and you cover all the sort of part of physiology behind the symptoms. And it works, it’s not a go one go-to drug. I can tell that much, you know, usually with a simple antiemetics and occasionally with benzodiazepines You accomplish exactly the same thing. But once again it just good for the lasers to know for the subset of patient, how a period is a viable options. But again don’t push it. Just just use the short infusion if you need to.

Jason Hine: Sure. And you’re doing that prior to your ketamine?

Sergey Motov: All simultaneously… At times prior to it, if you can if time permits. And if patient painful syndrome warrant, at least give you maybe additional 5 or 10 minutes break. Yes, I may start with haloperidol and then go full throttle with subdissociative aka low dose of ketamine analgesia for this very patient.

Jason Hine: Okay. Perfect. And so, I just want to pin down some of these numbers as well because we, we talked about, you know, we’re going through the spectrum and we talked about dosing of 0.1 to 0.3 milligrams per kilogram. That is our dose range. I want to talk a little bit about special circumstances and see if that affects that range or where you land in there a little bit. First, I’ll say elderly, you know, we talked a little bit about the use of ketamine for painful conditions in the elderly, as a nice alternative to opioids in these patients my go-to is the sort of right in the smackdown and not in the middle, but I say, in these patients, my go-to is 0.15 milligrams per kilogram. How are you guys dosing your ketamine for analgesia, in the elderly patient?

Sergey Motov: So if I may, I just wanted to reiterate one thing that doesn’t that you mention. Jason, 0.1-0.3 mg per kilo. It’s particularly year towards intravenous route or subcutaneous route because just to jump ahead of myself, I just want to cover this briefly and then I get to your beautiful specific judic element analges. Is that should IV access be unavailable or not timely accessible- intranasal route. It’s beneficial for management. Variety of painful conditions in Immerse department, paramila pediatrics. But there’s data supporting it’s used in adults. So for the intranasal route, we’re talking about 0.5 to 1 milligram per kilogram dose. Now just remember, you cannot push more than one mL per nostril. My prefer those in ranges 0.3to 0.5 ml. You can always split and titrate.

Jason Hine: Mmm, interesting.

Sergey Motov: If you do not like intranasal route, the next, which I have been researching for the past five years is inhalation route by using breath actuated nebulizer. Range 0.75 to 1.5 makes per kilo, but recent study, we did in my shop showed that there isn’t a different between three doses of ketamine given the nebulization. So 0.75 mgs per kilo giving by a breath actually nebulizer maybe useful, adjunct in situation when IV is not there, patient refuses to be poked in the nose. So consider utilizing inhaled route of ketamine analgesia. Lastly, data is not quite there yet. Oral ketamine has a very poor by availability, and I hope Ryan will support me on this one. But despite this it’s still fairly effective analgesia. Sata comes from the literature in patient with burn and post. Surgical traumatic post surgical amputation surgeries and for this reason we use injectable ketamine because oral ketamine is not neither approved available in the United States in the form of tablet, caplet as FDA goes, but you can use injectable form of ketamine from the vial and put in a cup and range between 0.25 to 0.5 milligram per kilogram given orally, just add a little sugar to it. Oral sweet because ketamine taste fairly bittery I tried it and that’s really, really bitter taste. 

So this is just overview. What are the routes and dosing? And I know we’ll put in a show notes, should you not have an IV? There are subcutaneous route, which exactly the same as an IV. There’s intranasal route, there’s an nebulized route and there’s the oral route.

Now geriatrics same principle know the drug nor the patient, that’s what the drug drug interaction, The physiology comes into the play. I’m a big proponent of starting lower range and add as I need to, but we do the start in geriatic patients, by given in 0.3 mgs per kilo problem is we use the intravenous push dose. And 87% of those patient were very unhappy with respect to feeling unrealty, but none of them had serious adverse effect that required either airway, manure, airway position in bands are there as opinion administration. So, technically, you can do at 0.3 mgs per kilo over 15 to 20 minutes. But to be safer, start at 1.5 see how they do. And if they do well, or they need more, just give another 1.5 so total of 0.3, but split in two.

Jason Hine: So Okay, perfect. So Sergey you’re saying in your elderly patients, you’re starting at the 0.15 milligrams per kilogram IV, and then re-dosing if you need to. Ryan, where do you land on the spectrum for your elderly patients?

Ryan Marino: I think the go low knowing that you can read dose is great advice because like Sergey said, I mean, you can’t take it away if you give too much, but you always have the option to repeat the dose. Ketamine has very fast onset. So, you know, if it works or if it doesn’t very quickly this isn’t something that’s going to be adding adding tons of time to your work and and your patients dispo and definitely if you could kind of avoid kind of some of the adverse effects as well, then then that’s probably the best approach.

Jason Hine: Perfect. And so, in terms of the logistics of that, how are you like when are you deciding to read those at what interval? Are you doing? Your reassessment and determination of second dose need or not?

Sergey Motov: So if we do in infusion over 15 to 20 minutes at the end of the infusion, you have all the rights to ask the patients, so but please don’t ask him by using the pain scale. So how is your pain? And would you like me to give you more analgesia? Based on the response engaging If you can find some objective finding to it should there be interested in additional those and you need to be very specific- Are you comfortable for a given another of this very medication? Do they make you feel well, bad and such and a patients. There’s no I feel good but I’m still having more pain than I wanted to be and I’m happy to get a second, those you do exactly the same thing. You got 1.5 over another 15 to 20 minutes and reassess at the end of the infusion.

Jason Hine: Ryan, you agree?

Ryan Marino: Yeah, I would agree with that.

Jason Hine: Perfect, all right. And so other special populations, you know, that for the analgesic dosing we’re talking about for adults. We’ve been talking 0.1 to 0.3 mgs per gig, we just reviewed elderly. What about pediatric patients? You have any dose adjustment when you’re using it for analgesia for ketamine, in pediatrics?

Sergey Motov: So interestingly, Data is not quite there yet on utilizing intravenous route of Sub Dissociative aka low dose analgesia when it comes to ketamine in pediatric patients, the primary route is intranasal. So, if I had to choose dose for intravenous route I would stick to 0.3. Mg per kilop, all I would use a higher spectrum for the fact that, as Ryan pointed out, kids are high metabolizer and you really kind of want to get their analgesic effect to them, and they seem to be tolerating ketamine much better than adults. Much lesser incidence of sort of psychoperceptual adverse effect, but the go one route is intranasal and the range is 0.5 to 1 and I would probably stick to one mg per kilo. I would do the top with upper limit of the intranasal route.

Jason Hine: Okay. 0.5 to 1 milligrams per kilogram for the intranasal route, when you’re doing it for pain. Okay. Fantastic. 

Ryan Marino: I love the discussion about the internal route because that’s something that’s so overlooked. And in patients who have any sort of limitation in establishing IV access. I mean, it is well studied, it is an effective way to administer ketamine. And if you need to either, get someone who is in too much pain to calm down or you just can’t get any other route. You can at least give them something for their pain while you’re waiting to establish some other form of access.

Jason Hine: That’s a perfect point and I think that like you said especially, you know, pediatric patients, you know if you don’t work in a pediatric ER, getting that iv, it can take a long time. In patients, when you talk about opioid use disorder, getting that point of access, it can take a while and so, to your point Ryan thinking about these other routes and and Sergey thank you for that great review of the different means of delivering this fantastic medicine and intranasal, nebulized, we talked about IV and we’ll talk a little bit more when we only get further down the spectrum about intramuscular as well.

In terms of our special populations just the last sort of areas to consider. Are you guys dose adjusting your ketamine for analgesia if someone’s already gotten lots of opioids? You know, say they have an acute fracture or they have something that’s incredibly painful. They’ve gotten morphine and they’ve gotten more and morphine and they got hydromorphone and now, okay, well we haven’t controlled their pain with these opioids, let’s use ketamine. Does your dose adjustment affected by the prior administration of those medicines?

Ryan Marino: For me I would say no. and this is something that is one of the situations where ketamine is most frequently used in the Emergency Department and is a great time to consider using ketamine when you have given someone all of your more typical analgesics and especially have given one or more doses of opioids and are not getting any sort of relief and the nice thing about ketamine because it is acting on a totally different receptor system you don’t have to work about any sort of significant potentiation or risk of kind of concurrent adverse effects, but you can kind of hit a different receptor and see if maybe that’ll help more for pain and especially in in the patients I see who have like opioid tolerance or just trying to avoid opioids, but people who maybe won’t respond to typical doses, usually don’t have the same kind of tolerance at their NMDA receptors that ketamine would act on as they would at their opioid receptors.

Sergey Motov: I agree with you, I do not change the dose. I love how eloquently Ryan put it together, I do the same dosing, I do the upper range of 0.3 mgs per kilo, and I do short infusion to it because it’s probably the safest medication in the setting for opioid on board. I would just emphasize that should there be a concern for again, you know, psychoperceptual adverse effect related to ketamine analgesia and you entertaining idea of using benzodiazepines, just be cognizant of the fact that if patient receive lots of opioids on board, you know, combination of opioids, and benzodiazepines may not be entirely kosher for some subset of patient who may have predisposition to have respiratory compromise. So for that reason, rather than just extended infusion, from 15 minutes to 30 into 45, and everybody is gonna be happy.

Ryan Marino: That’s a great point too because I think we, oftentimes do forget that what medications can interact. So if you were giving your ketamine with the opioids because it’s going to be a safe alternative. If you give the benzo with it, then you’re kind of setting up a whole new situation and the benzo plus the opioid is a problem. So I did really like how Sergey mentioned the use of haloperidol, or some sort of dopamine antagonist, instead. And in thinking of not to get like two into the weeds here, but the reason the ketamine has these psychosocial or psychological psychiatric perception. Disturbances it does have pretty significant action on your dopamine receptors and so particularly like D2, the same receptor pathways that we think of for like psychosis psychotic disorders. And in terms of just some medical history ketamine was developed and still carries the label of general anesthetic because it was one of the first anesthetics, but it replaced PCP, which was the standard anesthetic or phencyclidine, Which is now only known as like a street drug or drug of abuse. And so they’re very similar, they’re structurally analogous, but PCP was problematic, because it works so much more on the D2 receptors and so causes more of the the psychosis and those kind of adverse effects. But at the end of the day, they’re very similar ketamine works very similarly as well. And so, if you can block that in some other way, it’s you’ve always got options if you you think about the receptors

Jason Hine: Interesting. I do like that dive into that topic matter. So the dopaminergic properties and, you know, talking about haloperidol, probably droperidol, in a similar vein, that’s going to help mitigate some of those psychological or psycho disturbance effects or side effects of ketamine. If coadministered essentially.

Ryan Marino: Theoretically I don’t think I can say that definitively but that is the thought and definitely given the similarities to PCP that is considered to be the quote unquote problem with PCP. Why we don’t use it in medicine anymore.

Jason Hine: Okay, yeah, that’s fair to say it. Things can make sense on paper or in terms of an anatomy analysis of them, but don’t necessarily we don’t, you know, have the, the data as I understand it to, to definitively say that’s going to work, certainly a 100% of the time. But is often your guys is practice to consider some of these adjuncts to avoid some of the side effects from the ketamine itself. Fantastic.

Jason Hine:  All right, so we’re gonna step out of the pain area and we were talking mostly about that. Dosing range of IV, 0.1 to 0.3 milligrams per kilogram. Let’s get into part two. And procedural, sedation. So if you’re following along with your show notes, we are going to be skipping right over a couple dose ranges. We are going to be skipping past the 0.2 to 0.5 milligrams per kilogram, which is kind of the recreational dose for ketamine, which is not really part of our repertoire. We’re not really looking for that recreational side effect. And then we have the partially dissociative dose of 0.5, to 0.8 milligrams per kilogram. But it is important, if your listener and you’re sort of paying attention to what we’re talking about here, there’s overlap, right? That recreational dose of 0.2 to 0.5 mgs per kg overlap, some with our analgesics and as does the partially dissociating dose. So we need to pay attention to and part of why we got into the dosing and side effects when we’re talking about ketamine for pain. Moving into the full disassociation or dissociative dose. Usually here we’re talking about 1 milligram per kilogram dosing or higher. But it may even happen with 0.7 mgs per kgs. First of all, Ryan, is that accurate? Would you make any adjustments in terms of the endpoints of those dose ranges that I just mentioned?

Ryan Marino: No, I think those are what is cited in the literature. And the Dissociative Range is cited as 1 to 2 milligrams per kilogram, which is quite a large range, to be honest, which kind of gives you an indication. That this is not, not certain and every everyone responds differently. So, there are reports of people having dissociative effects at lower doses. I have seen people have disassociate of effects that even lower doses, than that. But yeah, those are the ranges. The good thing is that, I mean, ketamine is very difficult to have, like a true overdose from. And so, in terms of when you’re thinking about the dosing wall, like going low, going slow, knowing that, you can kind of repeat your dose much more easily than you can react to giving someone too much. There really is low risk of an organ toxicity or sort of end organ toxicity and kind of the problems that we worry about in an overdosing someone on a medicine.

Jason Hine: Perfect yeah. And I think that’s one of the reasons why we in the emergency department have loved it so much particularly as we get into that that realm of procedural sedation is- especially if you’re in a circumstance where you have to be giving the, you know, sedative and then performing the procedure, which is obviously never ideal. But some of us practice in single coverage departments, where this tends to or has to happen on occasion. Medications where you feel safe, right, where you don’t run the risk of an overdose or, you know, going too far off the end of a sedation scale is very valuable from just having confidence and the ability to focus on the other elements of the care you need to provide.  SoIt’s good to recognize that for you Ryan, you’re noticing as well. That one to two MiGs per keg, it can occur at lower doses as little site sort of 0.7 mgs per kg, but that’s the dose range and knowing that within that range which obviously there’s a, you know, 2x fold change in the concentration or amount of medication being delivered. It’s very hard for a patient to overdose on this medication. So for you guys, I want to know kind of what procedures do you think about are being best suited for a ketamine-based sedation?

Ryan Marino: Umm, I think in my world, when I most reach for ketamine for a procedural sedation, indication pediatric patients are probably number one because it is A- the most easy to use and readily available medicine that we have most of the time for, pediatric procedural sedation, and it’s also very safe and easy to dose and again given their higher rates of metabolism usually, can actually clear, clear quicker with probably lower lower risk of complication as well. But I think other situations where  I’m worried about an airway and don’t want to give agents like propofol or even automate that have more of a risk of respiratory depression. And then certainly situations where patients have more pain because ketamine has these great analgesic effects. It is really useful in sedation. When, you know that there’s going to be a significant component of pain specifically, like putting someone in traction for a long bone fracture. Anything like that. And I think in traumas, it’s very useful. Especially when you’re worried about airway blood pressure, risk of kind of hemorrhagic shock. Those kind of things. Anyone who is, is already in shock can benefit from from ketamine if they need some sort of sedation as well, just because it doesn’t really take away, the adrenergic drive that they have the same way as other medicines like opioids will. But yeah, I mean I think as Sergey said initially there’s really no one who is wrong for ketamine for procedural sedation. It’s just kind of thinking of each specific situation differently but the real exclusionary criteria would be pretty narrow.

Jason Hine: I like that and I like you sort of bringing it back around as well, right? So as someone gets that dosing, they’re traveling through that spectrum, right. They’re traveling through the other dosing ranges and the analgesia is there, we know that people kind of when we see them go down from ketamine, we see that sort of perceptual disturbance and then we have some emergence reaction because there’s a partial dissociation as they metabolize. So, it’s important to not forget that, as we increase our dosing, we are getting some of the effects from lower dosing obviously. So, the analgesic properties of ketamine used in the sedations makes a lot of sense to me. Obviously, you know, pediatrics completely agree. That’s one of my go-to’s in that regard, you know, insertion of a chest tube in trauma as you’re saying these sort of painful conditions, I&Ds of, reallyYou know, bad abscesses or abscesses in very sensitive areas of the body, where people can’t tolerate, just local anesthetic, is another consideration that all of that sort of jazz, with my practice. So first of all, thank you for confirming what I do and then secondly, I guess I’d ask when you’re doing your dosing here. How do you approach that are you, are you kind of starting on the one or the two big? Is it patient specific? Do you re-dose throughout the process?  kind of break that down for our listeners a little bit.

Ryan Marino: So for me, and this is just my own personal practice, this is not necessarily based in any sort of Like real evidence, but I will usually try to start on kind of the lower end with 1 mg per kg. Obviously, every situation is different and certain situations you can tell that you’re gonna need more than that. But having a repeat dose, there would also be my standard knowing that many people will need that the 2 per kilo, and then kind of giving it giving it slowly to start. And if you’re giving like a slow, very slow IV push or running it through a pump even, then you can really see how much you actually need and you have a less risk of the kind of apnea and and other things that we worry about.

Sergey Motov: I think I found procedural sedation is one of the greatest arts and the expertise of the emergency physician are gifted with. And it’s not just giving to us, it’s years of practice and polish on the craft and everything else. I am totally in agreement with everything you said respect to indications, forget him and utilization for personalization, I could muscle pain, reduction, closed reduction and, of course, pediatrics. A personal experience being that, I tend to use range of 0.75 to 1 especially when it comes to- 1 mg per kilo on ketamine-  And I do that very, very slow infusion. But I tend to add it little smidge of propofol and I tell you why, I usually joke that I use ketamine to induce and use propofol for smooth sailing. I found that if I do 10 to 15 milligram of propofol slow intravenous push before ketamine and then I do 0.75 to 1 and get them to the plane of being fully dissociated. Because partial dissociation is nightmare for a patient and physician, and then I can continue my give another 10 to 15 of propofol while. I may give myself extra 10, 15 minutes of longer duration of the procedure when they come in back, when they reemerging, they connect in their brain to sub-brain to feel it becomes much smoother. So the recovery period. I found it was much more pleasant for patient and physician. so I don’t know. Ryan and Jason, where you guys approach? Do you add propofol sub anesthetic dose or low dose of propofol to ketamine or do you just go as a soul agent?

Ryan Marino:  I really like that you brought that up because I do use them together sometimes and I know that it is a very popular thing in emergency medicine the like  “ketofol” combination and it is Interesting to note and also a good thing, I think in terms of kind of the risk benefit and safety profile, to talk about how when you do use them together you can use lower doses of both. And so certainly I mean propofol is the, the riskier medicine. You can get very good sedative effects with using much lower doses of both of those agents when they’re used in conjunction due to kind of their synergistic effects.

Sergey Motov: Yeah, I love it the way you said it. You know what my personal experience? I was always against Ketafol and until I do maybe I’m too too conservative. The notion of having two drug in one syringe always been against every belief in me because I have I like to have a control over a medication I give. If I have a drug mixed in one syringe, what how do I know what I’m giving? Right? So I the word “ketofol”- have a syringe with ketamine which is transparent, have a syringe with propofol, which is milk and use one of which, you know, two ml 3ml, but let’s have a control over. You know what we’re giving. The very notion of mixing two drugs, and then just hoping everything’s gonna be right was, I was against it from the beginning. and I’m glad you brought up ketofol business. I just hope people understand that makes into drugs and losing full control over it. It’s not safe.

Ryan Marino: Yeah, I am with you on that. I do not like when they’re mixed together in the same syringe. I always thought I was just being kind of overly picky but no, you bring up a very good point.

Jason Hine:  Yeah, it’s, I mean, it’s a, It’s a pithy way to describe the use of the two medications, but having them separate and using them and allowing them to mix in the human, make sense to me as a ketofol sedation and then Sergey you’re giving it initially as propofol followed by ketamine. When they start to emerge or you redosing the propofol or is there still an effect that many, you know, minutes later?

Sergey Motov: So what I do? Yes, I do 10 to 50 in the proper for 10 milligram of probable very slow, postal patient my burn a little bit, they get relaxed and then I, you know, give him ketamine and they’re very transition. Get to the Alice in wonderland, the cross and the plane, and the going to the other world. It’s much more palatable once they’re dissociated and we’re doing the procedure. I’ll give them another 10 to 15 or for the most part, that’s enough. So when they come in back the transition returning, it’s much smoother because we will see in patient going through this, you know, they’re trying to reconnect and they’re going through some emergence phenomena, some get agitated, some start screaming, some get, just crazy, look, what just happened to me? Propofol tends,, at least in my experience smooth out, and there’s just open up their eyes. And the man asks, What am I what happened to me? And it been very beneficial. That is my practice.

Jason Hine: I like it. I like it. I have not used the combined agents before I think I’m maybe a little bit too much of a purist in my own, right. But it’s something for me and and the listeners to consider as an option I just wanted to bring up specifically rapid sequence intubation and are you guys dosing in any different fashion or administering at a different interval or speed when you’re doing RSI?

Ryan Marino: Not typically I mean depending on the exact situation in terms of trying to have the like perfect RSI where it’s not really RSI anymore. I think 1 to 2 mgs per keg is what I would go for. I don’t think I am a dose adjusting  it. 

Jason Hine:  Okay

Sergey Motov: I do, you know, one to two. Usually it’s 1.5 mgs per kilo and it’s it’s a rapid push. This is the only entity when I do a very rapid push as name implies rapid sequence intubation.

Jason Hine:  Right. And in that way we’re you know part of what we like about the ketamine is is preventing apnea but we know that in these circumstances we’re ready to manage apnea. Should it be precipitated by rapid administration of ketamine. Alright, any other things you guys want to add to that sort of procedural sedation before I talk about takedowns?

Ryan Marino: Well, one thing I think that I didn’t mention that is a good time to use ketamine. And we’ve talked about, I mean, airway being like, a big reason to turn to or reach for ketamine. But in someone who you’re trying to do like a nasopharyngeal scope on or some other procedure where you need them to be, maybe dissociated or very very sedated, but don’t necessarily want to end up intubating somebody in your department. I feel like that that dosing of ketamine is also very useful and with the kind of rise of NP scopes in emergency departments, I think this is probably something that we’ll see more of as well.

Jason Hine: That’s a good point.

Sergey Motov:I agree. That’s a good point.

Jason Hine: Yeah, I was wondering a little bit about that and and I bringing ourselves to the sort of the conclusion of procedural sedation. We’ve talked a little bit about Different routes of administration. And so, Ryan, as you mentioned airway things we you know I had a case that we are talking about on this podcast and other episodes where we actually used ketamine to facilitate removal of a foreign body from the upper airway. And your NPL scoping I think is not dissimilar to that allowing for us to manipulate, get into the nares and the hypopharynx without really causing a lot of agitation or irritation to the patient. So my practice is increasing in the use of intramuscular ketamine for a version of procedural sedation, particularly in pediatric patients where IV access is challenging. I was wondering, if you guys have any experience with that recommendations or you know words of caution for that practice.

Ryan Marino: I don’t think so. I mean, you’re onset and duration might be both be prolonged but otherwise I’m not really changing my practice in terms of kind of monitoring dosing, anything like that.

Jason Hine:  Okay, that that’s confirming for me I think in and it certainly gets us sometimes into a position where you can move toward an IV or get your more secure means of management of the patient to you know deal with any quality that might happen from your IM administration but it seems to be a reasonable approach for, you know, getting a pediatric patient where IV access is not readily available into a piece place of, you know, either analgesia or sedation to allow us to to manage them more appropriately. 

And that’s a, I think a good transition into sort of our last area of conversation for me in the use of ketamine, which is part three, what I kind of called “the takedown.” And I wanted to end the conversation here essentially, the management of agitated delirium where this term the takedown is used for, basically whatever you know, you might want to call it the chemical takedown chemical or strength. I IM anxiolysis if you want to avoid the use of the term restraints in the chart, it goes by many names, but essentially we’re looking to have rapid acting sedatives to control a patient who’s in a state of agitated delirium so first I wanted to ask you guys how do you define agitated delirium or when you know, That a patient is experiencing this, right? I think drunk and annoying is one thing, but agitated delirium with its 30 to 40% morbidity mortality is is very different. So how do you sort the two out personally?

Ryan Marino: So this is a really controversial topic and I don’t think there is necessarily a good answer. And there’s a reason that agitated delirium is not considered a like true quote unquote medical diagnosis because of this and not to kind of like quote someone ridiculous here, but it’s one of those things where “I know it when I see it,” but I would say that when someone needs to be chemically restrained, or given like a sedative medication, they should be a danger to themselves and others without it and be at risk for serious harm to themselves or other people ad also not be in control of their own… Not have capacity, I guess would be a better way to phrase it.

Sergey Motov: Yeah, I agree. You know we got a belligerent intoxicated patient who screaming and yelling and seems to be aggressive but Conversing and may exhibit some evidence of understanding that, he’s just took too much of alcohol, and we just ask him to sit down and sort of follow commands. Agitated delirium, contrary you have completely confused person who’s a danger to himself, another mind you exhibiting some great aberration hemodynamics and totally detached from reality. And these are the people that we tend to act rather promptly on.

Ryan Marino:  And I think one of the things that gets kind of missed in a lot of these discussions, is that the reason this has such high mortality, is not because of the treatment. It’s the untreated or improper treatment of the quote, unquote agitated delirium. And so, if you look at the deaths, the 40% mortality rate, it is usually, I mean, because of the use of physical restraints, causing actual asphyxiation or people who are so hyperactive if they don’t injure themselves have some sort of other end organ damage just from things like rhabdomyolysis and and that. So ketamine itself is is very safe and is definitely preferable to those other outcomes.

Jason Hine: Perfect. I like that in terms of a transition and and taking a second to recognize that it’s not our management of agitated delirium, that’s killing people. It’s the agitated delirium itself right? It’s the tachydysrhythmias from the catecholamine surge or the rhabdo as you mentioned or other elements of their, you know, hyperthermia, you name it there. A lot of things that can lead to them or morbidity there, but it’s allowing them to continue in that trajectory, that’s problematic. So, Ryan you mentioned, it’s safe. Tell us a little bit, you know, are there that you hear about, which is a terrible way to recite the literature, but there are, you know, reports about intubation requirements upon arrival to the emergency department. When EMS or other personnel, given intramuscular ketamine, how safe is this? And you guys use it in your departments?

Ryan Marino: Yeah, so I guess you caught me there. I try to avoid using words like safe but when it comes to ketamine, I mean ketamine as far as medicines go is one of the safest ones that we have. And so, while nothing is inherently safe, at the end of the day, you can have problems related to it, I think ketamine has some of the, the fewest problems that we see and certainly is safer than kind of the untreated agitated delirium. Certainly there are special populations where you maybe want to worry more. And we talked about some of them, but I think in terms of like a high dose rapid push of ketamine, however, you’re giving it in someone who has like advanced cardiomyopathy, congestive heart failure or something like that, maybe is a little more concerning and there’s certainly a lot of concern within the anesthesia literature related to that. But overall, I mean, the untreated agitated delirium is, what kills people or improperly treated. And again, it’s much better than having six people hold someone down and sit on their chest etc. And at the end of the day that an organ effects from ketamine are are very low low risk of toxicity, reports of people who have ketamine administered and then have some sort of bad effect or end up in the emergency department needing to be intubated right away, likely have some sort of confounding and it’s also important to just remember that the agitated delirium, while not a medical diagnosis per se indicates that someone is having a true medical emergency. So whether it’s a drug overdose in their hyperthermic, they’re experiencing organ failure from that. That alone is the reason that someone could have a bad outcome in itself. And so I think it really is kind of each situation. It’s going to be dependent on on the specific situation, but is more likely to be a result of whatever underlying etiology and affects the agitated delirium then the ketamine itself because there’s very few situations where I could say you, if you add ketamine to that, you’re gonna hurt someone or If you add ketamine to what’s going on, that’s a sure way to kill somebody. Those kind of situations don’t really exist, which is why so many people will say that, the ketamine is so safe and why I would agree with that.

Sergey Motov: I couldn’t have said it better than Ryan. Thank you for doing this. And I wholeheartedly agree with you. You know, ketamine, it’s in my own experience and in literature support and everything else, just by those reports, it’s one of the safest medications and patients comorbidity and maybe some drug drug interactions, ingestion, what have you probably major role in the fact that somebody, you know, respiratory adverse effect may ensue but it’s solely attributed to ketamine. Ketamine, it’s fast acting, short acting, it just overall very beneficial drug. Probably top drug that should be used for this very indication such as agitated delirium..

Ryan Marino: And the discussion I think about agitated delirium and ketamine kind of gets muddy because of the fact that there are situations where it has been used as like a coercive form of restraint or been used inappropriately. And so that’s also something that everyone should be very cognizant of who is administering it and what situation definitely plays a big role. But in terms of kind of, at the end of the day, the drug itself is not toxic. You can introduce it in a way that is is toxic I suppose if you’re like holding someone down and giving them ketamine inappropriately, that that definitely is completely different situation.

Jason Hine: Well said gentlemen, I like that sort of summary of that topic and I it and it makes sense to me in that regard. I personally have maybe a biased perspective that, if when I think about the circumstances where someone comes in via EMS, having received ketamine intramuscular. And I think about the patients that I’ve done procedural sedation on using ketamine- If I saw that person in that state, come through, my department rather than being the one to put them into that state, I feel like my threshold for an intubation would certainly be different, right? My concern for that patient’s airway protection and ability to manage themselves is going to be slightly different and so I might be, you know, inaccurately describing those circumstances, but having someone come in in a state where they have been sedated with ketamine in that regard, similar to how they appear when we are doing their procedural sedation despite their ability to maintain their airway reflexes, that’s going to be alarming to a lot of ED physicians. So, to summarize what you’re saying, I think you’re our management of agitated delirium needs to be taken seriously, it is the agitated delirium itself, that is detrimental to people and are physical restraints, or production of rhabdomyolysis or hyperthermia that’s the problem. Ketamine is generally a great agent, we can use the term, probably safe agent for this use, and we don’t think we’ve mentioned the dosing as yet. So ketamine , it’s generally thought of in my mind, four milligrams per kilograms IM. is that how you guys are dosing this agent for this indication?

Ryan Marino: I think that’s a good like general approach. I’ve seen, I mean, two milligrams per kilogram intravenous push, five up to five milligrams per kilogram intramuscular. And again, as has been stated repeatedly, I think, if you want to go on the lower end, knowing that you can repeat it, certainly, in these situations, where maybe safety is a concern in using an exposed syringe needle into someone. You may want to start with four milligrams per kilogram intramuscular, but the really the risk of kind of overdosing someone. If you start, there is, is very low, if not completely negligible.

Jason Hine: Perfect

Sergey Motov: Yeah, I I agree with the dozen ranges, you know, three to five, probably average the most commonly used four milligram per kilogram. But once again, as long people, you know, listeners, understand the notion is individual approach. You can still give a little more if you need to but risks versus benefits. See the patient from the view and choose appropriate, those that will give you better benefit best benefit of, you know, chemical restraining, this patient in front of you protecting patients protecting your fellow colleagues.

Jason Hine: Excellent and within that- So we have that sort of three to five. If you say someone has you know kind of chewed through your more typically used intramascular medications 5 of droperidol pr haloperidol pair it all with two midazolam that did very little to, or for the patient. What are you guys dosing there? is it, is it still at that same number you do suggesting in those patients?

Ryan Marino: I would not dose adjust. I would probably maybe start with four or five rather than the three but would stay in the three to five range and knowing that in in those cases in particular, like maybe midazolam would be another good adjunct to kind of give with the ketamine or knowing that you might have to repeat it as well.

Sergey Motov: Yeah, same here. Not those adjustment. I would probably start with four.

Jason Hine: Excellent and my my last question having trained in North Philadelphia, seeing PCP, What if someone comes in high on PCP. Ryan, As you mentioned their analogous or they have, you know, properties that are very similar. Are you dose adjusting if you have someone who is “wet”, who’s high on PCP with educated delirium?

Ryan Marino:  So this is a great question and PCP is weirdly very, very popular prominent in the Cleveland area too, which it’s it’s very rare in the United States nowadays. There’s just very few pockets where people use a lot of PCP. I don’t think it’s wrong to give PCP (he means ketamine) if you’re trying to keep someone calm knowing that the dissociative effect is the the goal here if someone is agitated on PCP, it’s because they are not yet dissociated in terms of kind of overdoses and and talk stuff we always reach for benzos first. And I know I’ve mentioned midazolam, probably too many times on this podcast already, but you can always try, try benzos. But ketamine itself would not be a bad option and would actually, I think treat PCP toxicity if someone is is agitated and, and needs to be sedated, just knowing that you might again, have to experience kind of their emergence reaction, when it starts to wear off because the underlying problem is related to the same receptors that you’re, you’re medicating them with.

Jason Hine: Excellent, I like that explanation. And yeah, it makes sense, right? If we’re talking about that spectrum, we’re working our way down, we’re going higher and higher doses if someone’s on PCP, ketamine as an agent for management of that, pushing them just further down the k-hole for, as a colloquial term for it, is not a bad idea, there’s no contraindication there. You might sort of, I would imagine sticking that middle range of the intramuscular administration, but as we already mentioned in this podcast, there’s really not a poisoning that can happen with ketamine. You’re not gonna necessarily overdose a patient in that way, if they’ve had PCP as well as ketamine on board. So I appreciate that perspective and I I do love the fact that you are in a place where you experience some some PCP patients. Gotta love the wet patient. They are A wild bunch as it were.

Ryan Marino: PCP is a very interesting drug. I mean, I could Talk about it for like hours, but yeah.

Jason Hine:  Maybe next time we can we have another podcast on PCP, not that different than this one, probably. So anyway guys, I really appreciate it listeners. This has been obvious a bit longer of a podcast and I appreciate those who are sticking through to the end because ketamine is so versatile. It’s so useful for us and it’s rare to get such great experts with with varying degrees of expertise in different areas of this medication. So gentlemen, thank you so much for joining us. Take a look at the show notes as we go through all the different indications, dosing, and routes of use for ketamine. And again, thanks so much guys. I really appreciate talking with you on the topic.

Ryan Marino: Yeah, this was a lot of fun.

Sergey Motov: Thanks for having us.