Hi, everyone. So welcome to our monthly AAPMNR Pediatric Rehab Medicine Community Lecture Series. So we try to do this the second Tuesday of every month at noon central time. So today we are excited. We have a talk on intrathecal baclofen pumps in pediatric rehab medicine, and Dr. Andrew Skalsky will be talking today. He's currently the Division Chief of Pediatric Rehab Medicine at Rady Children's Hospital. He received his medical degree in 2003 at the University of Minnesota School of Medicine, and then his internship and residency training were at the UC Davis in PMNR, and he stayed on for a fellowship in neuromuscular medicine and peds rehab. He's board certified in PMNR neuromuscular medicine, peds rehab medicine, and electrodiagnostic medicine, and he's currently also a professor at the UC San Diego in the Department of Orthopedics. So I will let Dr. Skalsky take over. Right. Moving on. So I think to really understand baclofen pumps, I think it's really important to understand baclofen in general. So I think most of everybody knows that it's a GABA-B receptor agonist, and it's readily absorbed through the GI system when you take it enterally or by mouth. But only a very small portion of systemic baclofen actually crosses the blood brain barrier, and it doesn't diffuse across like most medicines do. It's actually dependent on an active amino acid transport system, which has a lot of genetic variability, even how well we can transport baclofen into the central nervous system. So, you know, we do super high doses of enteral dosing of baclofen, you know, 80 to 100 milligrams a day, and that pretty much saturates that transport system for most patients. So going higher probably is not really going to result in more baclofen getting to the brain and spinal cord, because that amino acid transport system gets saturated pretty quickly. So we know that, you know, enteral dosing of baclofen leads to pretty small CSF levels in comparison to the plasma levels. And because of that, you know, back in the 90s, they figured this out and said, well, let's come up with a way of bypassing the blood brain barrier and put in a pump then where we can deliver the medication directly to the cerebral spinal fluid and kind of bypass this whole amino acid transport blood brain barrier problem. And so, you know, the baclofen pump is just that. It's this implanted pump. Everything is under the skin, so it's all self-contained. Most often in pediatrics, we put them sub-fascially because we know there's less complications than that. A lot of times in adults, they'll just put it subcutaneously, but there is a higher rate of complications in kids if you put it subcutaneous versus sub-fascially. And then there's basically just a catheter that hooks up to the baclofen pump. It just tunnels under the skin around posterior to the back and goes in in the low lumbar space. And then the catheters thread into whatever level you want it to. And we'll talk about that a little bit later. The thing that I'm always, not always amazed by, but, you know, first in training was, well, why if we're getting way more baclofen then to the central nervous system, why is there so much less sedation with intrathecal baclofen than there is with enteral baclofen? And the reason for that is because baclofen itself is not actually all that sedating. It is definitely sedating, but it's not terribly sedating. There are two isomers of baclofen. There's an R and an S isomer. And the R isomer is the clinically active isomer, and it's not really metabolized. It's basically secreted, cleared from our system through the kidneys, and it's unchanged. It's the S isomer that's actually more metabolized, doesn't have any clinical benefit from a spasticity standpoint, but actually some of the metabolites of S baclofen cause sedation, and they do readily cross the blood-brain barrier, not through that amino acid transport system. And so that's where enteral baclofen and systemic baclofen actually cause more sedation than intrathecal baclofen, even though you're getting a much higher dose to the intrathecal space because we don't have livers in our CSF. And so the baclofen is basically not getting metabolized at all. And the only baclofen that is metabolized is the small amount, then, that is cleared from the CSF and gets into our systemic circulation, but it's such a low dose in comparison that we just don't see that same level of sedation with intrathecal versus systemic baclofen. And then, of course, just depending on the dose, it's a set reserve volume, so refills can be as frequent as once a month to every six to nine months, just depending on how much medicine the patient's using and how big their pump is. The batteries, it is a self-contained system, so the batteries do last on average about seven years. The battery life is directly correlated to the daily dose. So it doesn't matter on whether it's flex or continuous or whatever you're doing, the dose is directly correlated or the battery life is directly correlated to the daily dose. So the higher the daily dose, the lower the battery life and kind of makes sense if you're thinking about it, because the pump's just running that much more. So it's probably more like the battery will run the pump for so many cycles and you go through those cycles a lot faster, of course, when you're on a higher dose. And then the technical kind of criteria is, you know, 25 kilograms, but we've had quite a bit of success going a lot lower than that. The age to put a pump in a patient has more to do with the abdominal real estate and how much space they have between their pelvis and their rib cage and whether or not you can fit a pump in there safely, more so than anything else. So some institutions are more aggressive at putting them in, some are less aggressive. But in general, that's about what we use here. But it ultimately comes down to basically how, you know, if you had a really, really short, heavy kid, then you may not have the real estate to put it between the rib cage and the pelvis. If you have a longer, skinnier kid, you might have more space, but then you also have more risk of having the pump not have as much covering and having post-operative erosions and things like that that complicate it. So it's one of the most important things with a vacuum pump program is having two-way conversation with your implanter and having an implanter that is dedicated to the plan because that back and forth communication is so critical to a successful program. So kind of going against the rationale of why we use intrathecal baclofen, just because it's the only way to get a decent amount of baclofen into the CNS, which is where we want it to work. And so, you know, if you look at some of the literature that's out there, as far as checking CSF concentrations of baclofen, you know, a 60 milligram per day oral enteral dosing leads to, you know, about 24 micrograms per liter in the CSF space. So again, that's 60 milligrams, that's 60,000 micrograms. So just remember there's a thousand-fold difference. But a 600 microgram per day IT dose leads to, you know, almost 600 times or 60, yeah, 600 times greater dose. So if you kind of look at the dose compared to the concentration, intrathecal baclofen results in 5,000 times the concentration in this CSF versus enteral dosing. And that's why it does work so much better. And again, it's interesting that even though you're getting 5,000 times more drug into the CSF, there is way less CNS side effects, as I kind of explained, basically due to the metabolites of baclofen and how that works. So, you know, what are some of the indications for it? So one of the things is those that are having too many side effects from enteral baclofen. It may be helping their tone, but they're just not tolerating it from the sedation standpoint. And then the other patients that we often use it for are those that, even if they're tolerating the high doses of enteral baclofen, we just need more. And so that's the way of getting more baclofen to them. So there's been lots of publications out there on just kind of the efficacy of it, you know, improves spasticity, improves gait, improves quality of life. There's a ton of studies out there now in the pediatric population kind of showing its benefits and efficacy. And there's even been one showing, you know, cost effective treatment of it compared to hospitalizations, comfort, other medications and that sort of thing. The biggest cost, of course, is with the implant and the new pump. And then it goes down over that seven years and then it goes, jumps up again every seven years when you have a new pump put in. The other thing that's really important to understand with intrathecal baclofen is it's hard to understand the dosing and principles if you don't understand the CSF dynamics, because that's where the baclofen catheter is going. It's going directly into the CSF. So I don't, I'm older than a lot of you. And when I was in medical school, we were actually taught that CSF is just this free flowing current river. So it didn't matter where you put the drug in, because it was all going to circulate like a river and get to where it's going. And we know that is definitely not the case. There is a significant difference in concentration of neurotransmitters, metabolites, proteins within the CSF, whether you do like a cervical lumbar puncture versus a lumbar or a cervical spinal puncture versus a lumbar spinal puncture. There's a huge up sometimes up to 200 times different in the concentration of different neurotransmitters and proteins, metabolites in the CSF. So there is a definite difference and it's not this free flowing river where everything mixes beautifully. It's much more if you've ever seen any neurosurgeries where there's craniectomies and you're looking at the brain and see the brain pulsate. I mean, CSF is a pulsatile thing. So it's much more like an ocean tide where it kind of ebbs and flows. Yes, you get some mixing just like you would in the ocean, but it's not nearly as free flowing like you think of a river. And so there is a huge change in baclofen concentrations in comparison to where the catheter is. So if we just have a patient on a simple continuous dose, only five centimeters away from the catheter tip or two inches, there's only 0.5 percent of the same level of concentration as there is at the catheter tip. So you're not getting a very large distribution of drug from the catheter tip itself on just a simple continuous infusion. And so it's most the drug is sitting at that catheter tip and not really diffusing well throughout the spinal cord and brain. If you use a pulsatile or a bolus type dosing where you run the pumps as fast as they can go, you get a much larger distribution of baclofen from that catheter tip. So if you then do a pulse of the same daily dose, but do a pulsatile or boluses at five, that same five centimeters, you went from a point five percent of the concentration to 75 percent of the concentration. And then even going further out at 10 centimeters or four inches, which still is not that large, especially if you're talking about a lumbar catheter, it is still much greater, though. It's at 23 percent. So that's why there is some advantages. And we'll talk about the different ways of dosing baclofen. But that's why that's the differences between like a simple, continuous drip versus a intermittent bolus type system. It's just the CSF fluid dynamics. So talking about that, so what is the ideal catheter tip and infusion mode? Well, to be honest, the ideal catheter tip level is not proven. There's definitely people like myself that have strong preferences and theories, but there is an ongoing study looking at catheter tip location. But it's just a hard thing to do because every patient is so different. So trying to do like a randomized control trial, comparing different patients and different catheter tip levels is just so hard because it's hard to compare patients to patients and to do a trial within the same patient is really tough because then you have to do multiple surgeries on the patient, putting the catheter tips at multiple locations. So I can just give you a little bit of anecdotal clinical experience that I've experienced in that we've had patients who had a low thoracic catheter level and was going in for their pump replacement due to battery life and ERI. And we decided to increase their, redo their catheter to try to move it higher because you can't push it in deeper because of sterility and things like that. So you can only lower a catheter tip with using the same catheter. And so we put in a new catheter and with their new pump replacement. And initially we're going to do the exact same dose. They did not wake up after the anesthesia because that same dose going from a low thoracic level infusion to a high cervical level, they were functionally overdosed. So they were flaccid and not waking up. And we lowered their dose and they ended up leaving the hospital only on 40% of the dose they came in on, despite nothing else changing other than we took their catheter level from low thoracic to cervical. The only study that's kind of attempted to look at this, or it's maybe what I feel is the best study that's kind of looked at this, is a fairly old study where this neurosurgeon placed all of their pumps catheters blind. So he did not have fluoroscopy. And so he put them all in and put them all in kind of the same distance. He would just thread the catheter in, not knowing how far it was going or where it was going, and then would take pictures in x-ray afterwards to see where they ended up. And then he just kind of published his series. So as you can see, the majority of his catheters did end up thoracic. But if you kind of look at the trend from cervical thoracic to lumbar to sacral, you'll see that the lower the catheter was, the higher the dose the patient ended up on. And so that kind of fits exactly with what my clinical experience has been, in that the advantage of going higher is that you can use lower doses for the most part, because you're getting to the area of pathology. And so our goal is typically to get the catheter tip as close to pathology as possible. So if we're talking cerebral palsy or acquired brain injury, we're trying to get it to C1, so that with those boluses, we're getting that additional four inches or 10 centimeters and getting it into the brain where it can have potentially more effect. The other thing that is a big misnomer out there is if you're trying to get the legs more, do a low catheter. And if you're trying to get the arms more, do a high catheter. I can tell you all cervical catheters still improve the legs more than the arms. So I'm not a big believer in putting it to that level. I think if you only want to get the legs, then yes, you don't need to do a high catheter. But if you are trying to affect everything, you're not going to get more. You're still going to get a greater effect in legs than you are in the arms, even with a C1 catheter level. So we have a long history at our institution of doing catheter access port. That's what the CAP stands for, or side port screening. And this goes way back to having that good communication with our implanter, where essentially we had two patients that went just for their standard pump replacement for battery life. We thought their pumps were working just fine, no problems. But our implanter was very meticulous, and he wanted to make sure every time that there was good free-flowing CSF when he changed the pump and that sort of thing. And two back-to-back patients, when he thought he was just doing a pump replacement, he got in there and was unable to get CSF through the catheter. So then he had to scrub out, re-consent the patient, reposition the patient differently, because now he had to redo a catheter as well. And so basically what happened was, since those two patients, back-to-back, we decided to change our protocol, where we started to screen all of our patients before they were going for replacement to make sure that their catheters were patent versus not patent, because that changes the surgical planning and what's needed and that sort of thing. After doing that a little bit, we decided, well, this doesn't really make sense. If we're finding some that are not patent, why are we waiting seven years for them to need a battery change? Let's find that out right away. So we screened all of our patients back in, again, I assume we've been doing this a while. So we screened our entire population of patients back then, all 91 patients, and we actually found out that 16 1⁄2 or 15 of those patients did not have a patent catheter. And so we went through and redid all of their systems and the average postoperative dose, the preoperative dose for those patients who had pumps and had catheters, and we thought were working fine. They did not have, you know, acute withdrawal or anything like that, that was obvious, but their post-operative dose with better tone control was significantly lower than their pre-operative Baclofen, because they probably were not getting much of the Baclofen at all, who knows where it was going, and we'll show the results of that. But, so based on this, we started doing yearly catheter testing to make sure that pumps, the patients with pumps, that their catheters were staying patent. So of the 15 catheters, though, that were not patent, we really couldn't find a trend, so 10 were cervical, which was, you know, around 18-20% of our cervical catheters, 5 were thoracic, same percentage of all of our thoracic catheters, 14 of them were on boluses versus simple continuous, so that was, again, you see that the risk, all these risks were about the same compared to the thing that they had going on, so there wasn't really a well-defined risk factor for which ones were not patent versus which ones were patent. Of the ones that were not patent in, with side port screening, we did did it twice to make sure that it wasn't just a user error, that sort of thing, and we had to feel pretty comfortable that they were truly not patent before going to the OR, and several even decreased their dose before going to the OR, but all 15 patients had a confirmed non-patent catheter when they were in the OR, so the good news is we didn't send anybody to the OR for any false positives, and then other results of those, a third, so five, were broken. We actually found when we were in there that they're broken, and that's sometimes harder with the newer catheters because they're more radiolucent. The original catheters were much more radio opaque, and you could see these breaks a lot easier, now with the new one, it's a little bit more difficult. Seven were occluded, so we tried to aspirate, we weren't able to get CSF, but then we basically, starting from the pump, working our way around to the back, just kept cutting chunks off the catheter, and we eventually were able to get free-flowing CSF, and then we connected that portion of the catheter back up to the pump and got free-flowing CSF again. Why seven were occluded at some point in that proximal portion of the catheter, again, we had no idea, and then, and seven percent is essentially, you know, one patient, I believe, and then one or seven percent, again, there was a very obvious kink that would occur in the catheter, and then when we kind of freed up the catheter, their catheter became free-flowing again, but well, well, half, we had no idea, we had no idea why the catheter was not working, and they just got a new one because we couldn't find any obvious cause as to why it wasn't flowing. So, as you remember from the previous slide, you know, we started this, and you know, that, the screening of all the catheters, we did a one-time screening, that was back in 2012 to 2014, and then we eventually published that data, but since then, so we've been doing this now yearly on all of our patients for the last 10 years, and we have fairly recently re-analyzed that data as well, so you know, we, our population's growing a little bit because you tend to gain pumps over time, not lose them, so now we have 166 patients that have had backflowing pumps versus the 91 at that time, and so we performed 829 cath side ports, essentially, during that time, and, but we only found six true positive non-patent catheters in the new population after replacing all of those original 15. One very, very important point is that no infections occurred, so despite doing 829 side ports, zero infections, so when we started doing the side ports, a lot of people were concerned that we were, you know, subjecting the patient to undue risk of infection, and if they get an infection, you're talking meningitis, well, I would say zero out of 829 is fairly good evidence that this is a very safe procedure to do with extremely low risk of infection, as long as you're using, you know, the standard side port sterile technique and that sort of thing. The other important thing we found out was no catheters after being placed were patent, and then later became non-patent. They were either non-patent from the first time we checked, or there was a few changes where they were patents, but then they got a new pump, but not a new catheter system, but for whatever reason, after getting a new pump, but not a new catheter, the new catheter was no longer patent, and we had to revise it, and I don't know if that just has to do with how, with the surgery, they kind of shoved that excess catheter kind of in the pocket and behind the pump, and if things are kinking, or if it comes loose at the pump, it's really hard to know, because again, over half the time, we never actually figured out why they weren't patent, but the good news was we never had any patients without some sort of intervention, like spine surgery, or a having a new pump put in for ERI, where they went from patent to not patent, and so now our new protocol is we check patency after it's placed, and you can do that anywhere from, you know, one to three, four months after surgery, like we wait a little bit of time, just so there's not a, you know, worrying about a seroma, or things like that, that you have to deal with for the post-operatively, and make it more difficult to do the actual procedure itself, and what we consider normal is having at least one milliliter of clear fluid, and that's because the cap reservoir, the side port reservoir, and the entire catheter is about 0.4 milliliters, if you have the normal uncut catheter length, so we want to make sure that we, because several times, we could get a little bit back, but not more than that, so maybe we were emptying the little reservoir, and the proximal portion of the catheter, but we're not able to get that free-flowing CSF, so we want at least one ml of clear fluid to know that everything is patent, and working, and we're getting, you know, direct CSF back, and now we don't repeat it, unless they have their pump replaced, or if they undergo spine surgery, or some other like abdominal surgery, maybe where they had to move the pump out to do the surgery, or something like that, just anything that could affect the positioning of the pump, and the catheter, so it's very important, I think, for anybody that is doing a back of the pump program, to be proficient in doing these catheter access port procedures, one, as I've talked about with the screening, but two, it's also the one of the primary procedures you need to do, if you're suspicious that the patient is having withdrawal, because if a patient's having clinical withdrawal, and you do a catheter access port, and you can't get free-flowing CSF, most protocols that have been published, say, basically go to revision, and replacement, it gets a little bit more complicated, if you have a patient in clinical withdrawal, who does have free-flowing CSF, and unfortunately, we've had that a few times, and it's a little trickier to know exactly how to manage that patient, and what the next best steps are, but so the top one you can see is a pump, and then the bottom one is kind of what that schematic looks like, with the cover off, and you can see kind of the gears, and the reservoir, and the refill port, and you know, the electronics, and all that, but basically that little catheter access port is this teeny little hole at the bottom of a cone, and it's not much bigger at all than the actual gauge, the needle that you use to access it, so you really have to make sure you're perpendicular to the pump, because if you're going in at an angle, if you guys think about, you know, physics, or geometry, or whatever that is, if you're putting the needle in at an angle, it is a bigger oval than that perfect circle, so you really have to be perpendicular to the pump, when you're doing your catheter access port, to make sure you, once you get the tip of the needle in that hole, you can actually advance it all the way through, and then the upper right is what it looks like on x-ray, you can see these things pretty easy, so we like to have an x-ray of all of our patients, just to know where it is, so we can, when we're feeling, and things like that, because it can be a little tricky to feel, and using the template sometimes can be tricky, so just kind of knowing where it's supposed to be, based on x-ray, it can be a really helpful thing, and then you can even ultrasound over it, so you can ultrasound over it, and you'll see this shadow occur, so you can see the very obvious lines of the pump there on ultrasound, and then the shadow will occur, where the refill port is, as well as the catheter access port, this is actually a refill port showing up on the lower right, I couldn't find any good pictures of the catheter access port pictures, and so I clearly need to take some, because I didn't have any, but it can be a very helpful thing, if you can't really palpate it very well, to confirm where your catheter access port, or your refill port is, the one important thing is, you want to make sure that it can be beneficial to push on the opposite side of the catheter access port, because it's kind of teardrop shaped, to tip that catheter access port more superficially, or so you're not having to penetrate as much soft tissue, so you don't want to ultrasound it without any pressure, and then add pressure when you're trying to do it, because you're going to drastically change the position of that catheter access port, so we have someone apply some pressure to the opposite side of the catheter access port, to kind of tip that port more superficial, and then we ultrasound it, and make sure that person doesn't take that pressure off, and mark the skin, and it can be a really helpful way of finding that port, and then you're a lot more confident too, as you're probing around in there, that you're hitting the right area, at least starting from a good place, because this procedure is not easy, like it's tricky, especially the heavier the child is, so if they're super skinny, and you can see the pump sticking out of their body, like that kid in the top left, you can basically feel the catheter access port divot with your finger, and it's a relatively easy thing to do, and to be honest, most time I don't even use the template in a child like that, because the template can make it more difficult than just actually feeling the divot of the catheter access port, or the refill port, but that's just something you have to develop over time, and what's ever easier for you, and like I mentioned before, you really have to make sure that you're inserting the needle perpendicular to the surface of the pump, because if you were going in at an angle, you may hit that cone, you may be able to slide the needle into the very tip of the catheter access port, but you're not going to be able to fully advance it all the way through, because it just won't fit, and then we make sure, as I mentioned, that we get one ml of free-flowing CSF back to really prove that it is a free-flowing catheter. There are some patients that it is just difficult, and you can try, and try, and try, because of their size, it's just hard to find, and so we will then use fluoroscopy in some patients to really make sure that if we think we're in, and we're not getting free-flowing CSF, that we can, you know, fluoroscopically confirm that that needle tip is indeed in the catheter access port, then so we can call it a very, very true positive abnormal screen, and these are just ones that just take time and practice, so one advantage of us doing it yearly was that we got pretty good at it, but we also don't want to be poking patients unnecessarily if we don't need to, so the next aspect I wanted to talk about is some of the different infusion modes of intrathecal baclofen, so as I kind of went through those CSF dynamics before, that a bolus dose does change the distribution of baclofen within the CSF, and so I'm a big proponent of bolus dosing for that exact reason, not that it works better, it's just that it's potentially more efficient. You can get by with a lower dose, and then lower dose means less frequent refill intervals, and again that just has to do with that distribution of baclofen to your targets of where you're trying to get it, and so that, you know, almost all of our patients are on flex dosing just because it allows us to get by with a lower dose for the patient, and a lower dose means less frequent refills. There are a few patients who are on very low dose that we have kept on simple continuous just because their refill interval is already seven or eight months, we don't need to make it 12 or 15 months, and so we just keep them on simple continuous. A lot of institutions will start out on simple continuous, and then as the doses increase, switch over to flex dosing, and we don't do that here for a reason I'm going to talk about a little bit, and that's this. So as I kind of mentioned before, I think it's really really important for a successful pump program to have that good communication with your implanters, and so one thing, one of the biggest complications post-implant in baclofen pumps being placed is having a cerebral spinal fluid leak, and then that leak turns into, you know, a fluid-filled area that causes the incisions to break down through the skin, and once that happens, everything has to come out because now you have an opening directly to the CSF that puts the patients at risk of meningitis. So decreasing CSF leaks decreases pump explantation. I mean that is one of the primary reasons for pumps to get infected and explanted is CSF leaks, and so if you can do things to prevent CSF leaks, you're going to increase your perioperative complication rate with baclofen pumps, and so one thing we do is we put a abdominal binder on all of our patients post-operatively to put pressure over the pump. One, it can reduce some of the seroma formation, but two, because fluid just tracks to the area of lowest pressure, even if you have a CSF leak in the back, the fluid can actually accumulate around the pump because it tracks along the catheter, not inside the catheter of course, but along that false space that that catheter created, and it'll start accumulating around the pump and not necessarily in the back if that's an area of lower pressure. So trying to increase that pressure around the pump using the binder basically tamponades the leak, which helps it then try to close. The other thing we do is we do three days of bed rest with the patients flat, similar to like what you would do after a lumbar puncture in that period of being down. Well, this is a much larger hole than just a needle going in for a lumbar puncture. So we do three days of flat bed rest with the head down because again, we're trying to decrease that pressure of cerebrospinal fluid at that low lumbar back incision and leaking out because the more it's leaking, the harder it is for the body to close up tightly around that catheter and seal it off. But during those three days of bed rest, it also gives us a nice opportunity to aggressively titrate their dose. So our standard starting dose is 96 micrograms a day. And the reason why we pick that is, you know, some institutions will start at 50 or 100 or whatever, but essentially at 2000, if you're at a 2000 microgram per ml concentration, which is the highest currently available concentration of baclofen, the lowest, slowest you can run the pump is 96 micrograms a day. So with the kind of goal of being that most patients are going to end up on that higher concentration, that's where we start out. And then we slowly start adding boluses or flex mode. And we just start with a one microgram bolus. And then four hours later, they get a two microgram bolus three hours later, they get a three, et cetera, et cetera. And so what that allows you to do is that not at any one time, are they getting a huge increase. But in the first day, you go from nine functionally 96 micrograms a day on their simple continuous all the way up to 132 micrograms a day, when you include that six microgram bolus that they're getting after that sixth bolus, you have to make sure you reprogram their pump, though. Otherwise, you're just gonna start the process all over again, because you can perform you can program the pump to do 24 hours. So as you can kind of see, this is a patient that we did in that they came out of the OR, they got to the floor around noon. So by the time we got the programming them, their first program bolus was at 4pm. So I don't know if you can see my pointer. But this is the one microgram bolus at four, two microgram bolus at eight, the three microgram bolus at midnight, and then etc, etc, all the way till noon the next day. So we have to program their pump between noon and four, or it's going to start all over again. Now you can also program it earlier and just keep that, you know, noon bolus the same and progress from there. If that's what works out for your rounding schedule, you just can't let it lapse into where it's starting all over again. But by going up, you know, ones and day one and two, you know, you're getting that 37% increase the first day at 27%, the second day, and then often on day three, depending on how close we are to goal, we'll start going up by twos. And so that day, you're actually getting a 43% increase, which most people just doing a straight one time increase, most people aren't going to do a 43% increase in one day, just because they're getting that 43% increase all at once versus spread throughout the day. I should back up a little bit because I skipped over this. But the reason we do Q4 boluses is we've just played with it a lot. We found anything longer than that, some patients will notice like the bolus on off effect at Q4. We haven't had any patients that notice it, it seems to them like it's simple, continuous. We are some patients that we've had on Q3 just to change it up. But anything we have at most of our patients, when you've tried to go to five or six hours in between boluses, definitely could tell like tighter, looser, tighter, looser type of thing. But we just don't see that with Q4 and it ends up being functionally like they're on a continuous dose as far as they can tell from their body standpoint. And it just ends up being a slightly more efficient. So this is why we start most of our patients on this flex mode right away. It's mainly because we can titrate their dose and get them to a good, decent dose by the time they leave the hospital, which saves them a ton of follow-up visits to come to clinic. I mean, if you would have done this doing 15% increases, this is the equivalent of 7 clinic visits. That if you would have done a 15% increase to every clinic visit to get to 240 from 96, it would have taken 7 visits. So that's 7 visits that the patient doesn't have to come back for. And again, this is if you're doing the programmer, this is what it looks like. You can program the time. We make our durations as low as possible because again, just trying to think of that CSF fluid dynamics, the lower the duration, the faster the pump's running and the more distribution from that catheter tip you're likely to see. And so this is programming that 4 a.m. dose that you can see is kind of pink there to be a 4 microgram bolus and we're just running that over one minute. As you get to higher and higher boluses, it'll make you increase the duration because you'll get to where the pump can't run that fast. So to get to a 20 microgram bolus, you might have to run it over 3 minutes, but the programmer will tell you all that information if you've got exceeded what it can do in that one minute time. So complications. So unfortunately, that's probably the biggest downside of back-lifting pumps is it's a surgery and it's a surgery that has complications. Things that have been identified as risk factors for complications is patients with CP with ASHRAE scores greater than 3. Probably not a ton of patients with ASHRAE scores lower than 3 that you're putting pumps in, so that's a tough one. Young patients. The younger the patient, the higher risk of complication. And that's probably just physically a geography thing. There's just not as much space, so you're putting the pump in a tighter space. There's less skin to cover it, so it's tighter, things like that. And there is, as I mentioned before, depending on your technique, sub-fascial versus subcutaneous, there is, and the institution, this difference around 5 to 10% of post-operative infection rates that do require explantation, and that's not fun for anybody. I can say thankfully for our institution, it's quite a bit lower than that, but that's what the published literature is. And then there is 8-year survival rate basically showed no difference, pump or not, and no increase in mortality, and that's for Dr. Kroc out of Gillette that she published several years ago. So it is a beneficial thing and one of the best ways to get baclofen to the CSF. There's a lot of talk about baclofen pumps and the change of scoliosis over time. I'm not sure this is an entirely answered question, but we do know that there is progression of scoliosis prior to skeletal maturity, and there is a possibility that the baclofen pump can increase the progression of scoliosis. And I believe it, in all honesty, I do think it's a thing, because we think in neuromuscular scoliosis, the main driver of scoliosis progression is weakness and not spasticity. And so if you're reducing their spasticity, you're probably potentially making them slightly weaker as a result, and that might be progressing their scoliosis. But I would also think that if you look at the patients, the number of patients that end up with spine surgery because of baclofen pump that would have ended up not getting spine surgery, I think you're talking an extremely low percentage. And like the number needed to not treat to prevent scoliosis surgery, if we want to do it statistically that way, I think would be very, very high. So you're withholding treatment from a lot of patients to try to prevent one patient from getting scoliosis surgery that otherwise you guys wouldn't have. But as there is another paper, though, that also shows that there isn't any change with progression of scoliosis with baclofen pump placement. So there's both publications and camps out there. I'm more in the camp, in all honesty, that it probably does increase the risk. But also, you're talking about a population that's at extremely high risk anyway. So the actual number of patients that you would have to not treat with a pump to prevent spine surgery, I think, is really, really high. So in my opinion, I'm not sure it's really a huge factor to consider. And of course, one thing we really need to know about with baclofen pumps is what do we do when they're in withdrawal? And I think we're all pretty familiar with training that baclofen pump withdrawal, we're going to see increased tone. We're going to have itchiness or pruritus. You can have hyperthermia, perspirations, agitation, trouble sleeping, or insomnia. If their tone is bad enough, you're going to get increased CK. That CK is going to spill over into their urine with myoglobinuria. And the primary reason that it can be so severe is if you have enough muscle breakdown and you're in rhabdo, rhabdo itself can be life-threatening and baclofen withdrawal can be life-threatening for similar reasons. The other thing that I think we're all familiar with with anybody having taken call is every time a patient with a baclofen pump or a BP shunt walks into the emergency room, we're always told it's their shunt or their pump. And we know it's not always the shunt or pump. But it is something that has to be excluded. So do the symptoms fit? And what other things have been evaluated? So not every single patient do we work up. But if a patient comes in and their CRP is entirely normal, but they have a fever and their waist more spastic than their baseline, you better look at the pump as a potential source. Now, if they come in and their CRP is elevated and they also have a fever and their white count's elevated, I would start digging around for other causes like a UTI or pneumonia or whatever the case may be before we start blaming it on the pump. How do we treat acute baclofen withdrawal? So basically, the principle is get as much baclofen to them as possible. But that is sometimes not difficult because it's not like we can just put in a new lumbar drain and start pumping them with intrathecal baclofen and bypassing their pump system. So we give them as much enteral baclofen as we can. As you all know, there's no IV baclofen available. And then you can also supplement with other GABAergic medications like benzos. You can use dantrolene to decrease the tone and decrease rhabdo by, you know, peripherally decreasing tone using other central nervous system antispasticity medications like tizanidine. One medication that has been well-published now that works really, really well to acutely stop ITB withdrawal is dexmetomidine or Presidex. I mean, it will stop it very quickly. Unfortunately, it causes sedation and respiratory depression. And if you have to titrate the dose high enough, it may result in intubation, but it will stop their withdrawal. And it works really, really well for this to get through that withdrawal period. But of course, it requires, you know, an ICU level of care and there is that risk of, you know, the patient requiring intubation if you do have to push the dose high enough to truly stop their withdrawal. So it becomes a balancing act. But just Presidex alone requires patients, you know, most likely to be in a more intense level of care setting to be monitored, that sort of thing. The other medication that's very often used in the withdrawal setting is ciproheptadine to help with the poritis involved with the withdrawal because that is sometimes the symptoms that actually the patients are most bothered by and the most uncomfortable because they are just in total body severe poritis, itching and scratching does not help. And it's a very, very uncomfortable situation for a lot of patients. There is an alternative. And so we kind of came across this at our institution. So there was a publication that you can see below of where they took sheep and they actually found that baclofen in sheep crosses the blood-brain barrier pretty readily, both the RNS forms of it. And so that inspired us to try nasal baclofen in the acute withdrawal setting. We essentially know that when you administer medications nasally, that you directly bypass the blood-brain barrier and therefore you don't have to be reliant on this amino acid transporter that, you know, is crossing the blood-brain barrier of the baclofen normally. So one thing that we tried in a patient with acute withdrawal, so he had a pump replacement. Unfortunately, we got greedy and tried to increase the size of his pump and he had a bunch of previous abdominal surgeries. The skin on his abdomen was not good and going from a 20 to a 40 ml pump in hindsight was not a good choice for him. And basically his skin just broke down over the pump. It just couldn't handle that extra pressure and stretch on the skin. And so a couple of weeks after it was placed, it basically eroded through his skin. We explanted it before it got that bad, but he went into terrible withdrawal and even there was some infection happening as well. But we basically could not control his tone and his spasticity and agitation and everything after it had to be explanted. And he was in the ICU and the only way they could do it was with the Presidex and that controlled it. But every time they tried to wean it and lower it, his tone would get so severe that they basically couldn't ventilate him because he was intubated at that point. And so we were struggling to progress towards extubation. And the ICU team is desperate because this was several days out now. And yes, the tone probably would have subsided at some point, but we were trying to speed this up. So we basically took the test dose of intrathecal baclofen and administered it intranasally and it worked beautifully. This patient has been on intranasal baclofen using intrathecal solution for four years now at home without the need to reimplant his baclofen pump system. So intranasal baclofen can be an alternative for the withdrawal setting. And the nice thing is it also can be an alternative if patients are NPO and can't take enteral baclofen. Similar to intrathecal baclofen, you dose it much more like intrathecal and not enteral. It's not weight-based, that sort of thing. There's not an oral-to-nasal or oral-to-ITB conversion that you can really do. So just like in an ITB patient that you are first placing the pump in, you basically have to start out low and titrate to effect, but these are the doses that we have kind of found work well. So again, similar to intrathecal, you can use way low doses because you're not getting that whole systemic circulation and you're bypassing the blood-brain barrier. So if they're really little, we only use 100 micrograms. If they're over 1, we start at 400 twice a day and just titrate by 400 micrograms every day until we reach clinical effect. And that can be really, really helpful for those patients on chronic baclofen that have a GI surgery or things like that that are admitted or NPO that you have alternatives to give since there is no IV form of baclofen at this time. And like I just mentioned, there's not really a great conversion. Based on a dosing we've seen over time, though, if you kind of remember on the first slides, kind of intrathecal to enteral, you know, like a 5,000 times difference. I think we're talking about a 250 difference when you're looking at nasal to enteral. So, you know, intrathecal is still, you know, 20 sometimes stronger than nasal, but it is it's in between the two. Another very important thing to be aware of as you finish fellowship and get out into practice is there's this great resource available to all of us. It's the Pediatric ITV Network started by Kristen Buxton there at Boston Children's who runs their program. And it's a Google group and people post questions to this all the time. It's you can post your own patients questions. You can read other responses. But it's a great resource to several of us that are members to it. And you get you know, you can get kind of consensus feedback and ideas and problem solving and things like that from from your Peds ITV community. All right. With all that said, I wanted to leave some time for questions, and I see there's some in the chat, but couldn't really open them. Only one screen today. So let me look at them now. That was fantastic. Thank you so much. I think we have a question about the ceiling dose of intranasal. Yeah. So that just got to that now. So because the ceiling dose ends up being not the chemical or the medication effect of the dose, it tends to be more of the real estate that you're limited to. You can only put so much liquid up someone's nose. And so we've kind of found that in, you know, a eight year old plus that about one M.L. is the most you can kind of administer at any one time. And even that's probably still going to get you're going to lose some medicine from a dripping out. So we use the two thousand per one M.L. dose, give half an M.L. to each nostril using a nasal atomizer. If you use any intranasal medications now, those atomizers readily available. And so we start out BID, but you can. The only way to go higher is the dose is to increase the frequency because of that difficulty with real estate. So we have some patients in really severe settings like a new brain injury and they're storming and things like that, that we're dosing sometimes two thousand every two hours around the clock. And there it's a patient in the ICU, that sort of thing. Now, we didn't start there, of course. We started at the same four hundred twice a day and just increase their dose pretty quickly based on what their effects were and what they needed. But that's that's kind of a ceiling dose. And you're not going to run into for the most part as you titrate quickly. You're not going to run into the medication overdose. You're going to run into just difficulty in getting enough medication in the nose, in all honesty. There will be a lot more coming out about this at AAPMNR and ACPDM and things like that in the future. What is the highest dose you have for a patient for daily intranasal baclofen? So in the outpatient setting, eight thousand a day or ten thousand a day, so they're doing two thousand, but they're doing it five times a day. And again, that's not they're not reaching like the like higher, they're not getting sedated from that or their tone is flaccid. We don't need to go higher. That's more. That's just the most we can really get in their nose, in all honesty. So and families don't want to do something, you know, every two hours. And so and similar to, you know, the intrathecal forms of baclofen, it's harder to get a higher concentration of baclofen because it will precipitate out a solution. And then when you have, you know, little particles of baclofen, you can't get them to flow through an atomizer. So you can't let that happen and it'll cause nasal irritation and that sort of thing. So that's about the highest and it's more limited, again, just on the real estate of where you can miss the medication to versus the effects of the medication. But the beauty of it is similar to intrathecal, you don't have the sedation side effects because you're not getting the systemic circulation of the S baclofen. So it's way less sedating than entero baclofen, similar to how intrathecal is so much less sedating. I'm curious for your post implantation titrations who it certainly seems like rehab medicine is pretty involved. I'm wondering what the logistics of that is. Is that your consult service managing that? Yes, they for the most part stay on the orthopedic. We have an orthopedic surgeon, a spine surgeon that implants our pumps. So we're a little bit unique that way, too. But I know there's several other institutions starting to use pediatric ortho, too, for pumping plants. And of course, neurosurgery is the most typical, but they stay on the implanting surgeon's service for those first three days. And we're consulting and titrating and things like that. If we want to keep them longer and they've kind of cleared them for discharge from a. So after three days, we allow them to start getting up and make sure they don't have signs of CSF leak, headache, things like that. And if they at that point are cleared for discharge then. But the family wants to stay longer or we want to keep them longer to further titrate. Then we'll transfer them to our service to then do that. But if they're on a good dose and want to go home, then they go home directly from the implant or service. Check in for any other questions right now. I think we are all excited to hear more about intranasal baclofen in the upcoming conferences. It's really exciting. Yeah, it doesn't, I mean, again, I can tell you it's not nearly as strong as intrathecal, but obviously there's not surgery involved, so there's advantages for sure. Yeah, I'll definitely give another boost to the Google groups. As an early career physician, it's been great. I mean, it's like reading case reports. It's so educational and interesting to follow along those discussions. And Kristen also hosts a yearly baclofen pump conference that is free in April, every year, I think, usually April. Sounds about right. It's a great conference that's offered both in-person and Zoom, and I agree. Thanks for mentioning that. I forgot to mention that. It's a great conference to go to if you're either in-person or over Zoom. When can you get a free conference? All right, well, thank you so much. We really appreciate your time. This lecture was fantastic. No problem. Look forward to seeing everybody come to San Diego for AAP MNR. Thank you.

intrathecal baclofen pumps

pediatric rehab medicine

baclofen mechanisms of action

dosing and delivery challenges

blood-brain barrier

intranasal baclofen

CSF leaks

collaboration in pediatric intrathecal baclofen network

post-implantation titrations