SCCM Resource Library-Two Teams Come Together: Intersection of Adult and Pediatric Care

Video Transcription

Hello, everyone. Welcome to this session. The topic is two teams come together, an intersection  of adult and pediatric care. I am the moderator of the session. My name is Ndidi Musa. I'm  a pediatric cardiac intensivist at Seattle Children's Hospital and a professor of pediatrics at the University of Washington. We have three topics to be discussed, adult ventricular  assist device for pediatric patients, adult drugs for my pediatric patient, and off-label use and this monitor doesn't fit my little patient. Please relax, sit back, and listen.  And at the end, we will have a question and answer period. Thank you.  Hello, I'm Amy Jennings. I'm here to talk with you today about adult ventricular devices in pediatric patients. I am a nurse practitioner practicing clinically in the cardiac ICU at  Seattle Children's as well as an advanced practice provider manager at Seattle Children's Hospital. Disclosures. So just want to mention I have no conflicts of interest, financial  or otherwise. I do present trade names and products here. It's part of the nature of describing ventricular assist devices, but I am not incentivized financially or otherwise  by the companies making these devices. And as a speaker and faculty, I do receive a discount  for SCCM course registration. Objective. Our objective today is to identify the limitations  of applying adult-based technology for heart failure. And specifically here, we're talking  about ventricular assist devices for pediatric patients. So as we introduce the topic, some things to highlight about ventricular assist devices are that technology for pediatrics  is far behind that for adults. And this is true of not only ventricular assist devices. There's just simply not the same market or demand in the pediatric realm as there is  for adults. And so margins for companies designing these products are quite small margins. As well as bringing a pediatric device to market, which has a little bit more complexity  and a time lag due to the number of patients required to be enrolled as subjects to endorse a specific product or treatment. So where does this leave us as providers when we have  children presenting with a need for mechanical circulatory support? Well, we have to be willing to be unconventional. And I'll present a few descriptors here in the literature about  ways to have adult devices work for pediatric patients. We also need to share and publish.  So two ways to do that are the PDMAX registry, which is an NIH-funded registry of mechanical  assist support devices, and the ACTION network. ACTION standing for the Advanced Cardiac Therapy's  Improving Outcomes Network. This is a multi-center learning network for pediatric centers that  implant, manage, and study patients with mechanical circulatory assist devices. And that's true  for children as well as adults with congenital heart disease. So a really robust network to contribute to. Big news to mention today is that recently the HeartMate 3 was approved  for pediatric use, and that had traditionally been an adult VAD, but has found to have a relatively favorable safety profile as compared to other pediatric VADs and is now approved  by the FDA. A couple of things in the works, HeartWare and Jarvik 2015 are other devices for whom the pediatric gap should be closing.  All right, so digging a little deeper into the limitations of these devices, I highlighted a few  things on this slide. Of course, size, weight, and body surface area are a big limitation. And  on the slide is a table pulled from Berlin Heart X-Core catalog describing here the various pump  sizes that one might select for young patients in contrast to the pump output delivered by these  devices. And I think this Berlin Heart uniquely has multiple size devices for pediatric population  as opposed to the other manufacturers of durable devices. What they show here in this table is a  bit of overlap between the sizes, but also the actual cardiac output that would be generated  by the devices as compared to body weight of the patient. When you get to that lower body  weight range, less than five kilos, there's significant bleeding, stroke, and hemolysis risk  as compared to patients above that weight, and that has been problematic historically in the use  of these devices. There are also complexities in pediatrics related to anatomy and specifically  congenital heart defects whereby the anatomy of a heart might make it very complex for a surgeon  to implant a device in an ideal, in the way it was intended for implantation. And so we'll talk  again about modifications there. And then having the pediatric world be such a small population or  relative sample size as compared to adult means it takes us quite a bit longer to really gain  experience and share knowledge in the use of these devices for our pediatric population.  Digging a little deeper into the elements of size, weight, and BSA. So on this slide, I made a table.  The devices in red, which are Berlin Heart, Jervic 2015, Medtronic, HVAD, and Heartmate 3. It's not everything, but those are four of the devices that are considered durable VADs  for which we've had published use in the pediatric population. Also in that table, I've included the Syncardia or Total Artificial Heart, which really has been made for a small  adult, not specifically pediatric, but of note found in the literature, BSA range of 1.16. So  that's a little favorable for an option for us. And then in blue, PDMAG and Impella. Those are two  temporary devices that are intended for pediatric use. I've tried to represent these devices on  the slide, but I'm rounding out the conversation about the table. So you'll see a BSA range for  Berlin Heart, and that goes quite low to 0.33. That's in their instructions for use. But again,  as mentioned, anything less than five kilos is pretty high risk. Sorry to jump between BSA and  kilogram weight, but that's how things are published. And then I'll simply mention that an Impella range, considering the extension of the device from inflow to outlet,  there is literature supporting the use of Impella for a BSA roughly 0.89. That would be the lower  limit. On this slide, I pulled a few devices just for visual representation. So at the top here is  one of the JARVIC devices. Over in this upper right corner, the total artificial heart.  Impella here in the center with a inlet port and an outlet port, and that seats  ideally in the left ventricle and out into the aorta, although there's also a RV or right side  configuration that we'll talk about. Over here, we've got the HeartWare. As you see, that's  implanted into the apex of the ventricle, inserting into the aorta. This is the Centramag, another  temporary device which would seat externally for pediatric patients. PDMAG is their pediatric  version, their smaller version. And then here are the various Berlin heart pump sizes, and these are  all extracorporeal as well or paracorporeal. Size is not the only consideration as far as positioning a device, but there's also a consideration in regard to the technology  housed in these devices. And I'll use JARVIC as an example. The JARVIC 2000 was created as a device  for use in infants. However, in ex vivo sampling or studies, it was determined that the device was  creating quite a bit of shear or hemolysis. So the company redesigned their pump and increased  the or upsized the outflow portion of the pump and created the JARVIC 2015. And that's the device  that proceeded to pumpkin trial. All right, so we'll go in a little bit to anatomy and modifications  here. So I've pulled five or six articles describing some modifications. Starting at the top,  there is something called bipella, and essentially it's the impella, and I showed you that on the  prior slide, but the impella used for both systemic and pulmonary output. So you consider that a  Bi-V configuration, and Encola et al. out of Columbia, as well as Lassa et al., both very recently  published their experience with this Bi-V configuration. So in Encola et al. publication,  they had a series of three teenage heart transplants with acute rejection who were supported  for just under two weeks, and they concluded that Bi-Val is a viable option for temporary mechanical support in pediatric patients with significant graft dysfunction. So those three  pediatric patients did recover or show improvement after that time on support. The publication  by Lassa et al. in 2018 described two teenage patients, both prior heart transplant patients,  with acute rejection and refractory shock. One recovered and was retransplanted, and fortunately  one proceeded to ECMO and did not survive the event. Modifications considered for Fontan can be unique, so that's an example of single ventricle physiology in use of a VAD system.  One of the challenges with Fontan is of course in most Fontans the RV is the systemic ventricle,  in all Fontans there's a single systemic ventricle, and seating the device into the RV can be problematic as it's oriented to the AV valves. And so there's two publications  that describe the positioning of a VAD in the right ventricle plus minus resection of the AV  or atrial ventricular valve to allow good inflow of the pump. So Rainey et al. out of Duke described use of this configuration in an eight-year-old 21 kilo BSA 0.84 using the  HeartMate 3 with excision of the tricuspid valve to present like a suction or inflow occlusion.  And the radiograph or x-ray just shown here is from that study, and the pump was positioned in  the hemothorax, which is also a variation. The pump is intended to be in the pericardium, but such a big pump relative to such a small size meant that they essentially had to  position this in the left chest. The patient did have three reoperations for bleeding,  but survived, went home, was subsequently transplanted 10 months later. Another publication  here for reference is by Nandy et al. using the HeartWare device in three patients, and they also  describe excision of the AV valve as a means to best seat the device without inflow obstruction. Two of those patients were less than four years old with BSAs of 0.58 and 0.62. So  this sample describes a technique that might allow for device implantation in infants and young children who might otherwise have been thought to be too small for such support.  And then a third modification to describe here is use of the ventricular assist device for patients with hypertrophic cardiomyopathy. Essentially when a patient has hypertrophic  cardiomyopathy, the ventricular mass is so thick and the ventricular cavity so small that a device into the ventricle, as these devices were intended by design,  would cause collapse and would not fill effectively. So the modification described by Dykes et al. and other centers are doing this, but modification described by Dykes et al. is  positioning the ventricular assist device in the atrium. And so atrial cannulation plus minus use  of a Gore-Tex graph can enable the device to be used as a circulatory support without and avoids  the challenge of the ventricle collapsing upon the inflow portion of the device. Lastly a modification which isn't listed on this slide is simply to say that some of these  externalized devices will allow for addition of a CRT circuit or even a oxygenator circuit.  PDMAG is a good example of a device that can be used for those modifications.  This slide depicts excision of atria and ventricle and this is a study by Woods et al. and they  described doing this for five patients and configuring a type of total artificial heart support. In their study they described doing this for with use of either Berlin heart or the  PDMAG and they report that three of the patients survived to transplant and were discharged home.  So they described this device modification essentially where they've excised the main portion of the heart, put in the cannulas to position using Gore-Tex graph to connect cannulas  to the main arteries, and then have externalization of the cannula for the actual pump housing mechanism and were able to support patients with this configuration.  On the horizon, so what are we looking forward to? Well already happening is some tests for virtual implantation using 3D modeling. So there's a group in UT Southwestern  and this is published or in press by Davies et al. looking at virtual reality so like simulated  implantation of using some 3D reconstruction and cross-sectional imaging. And for this group, the two pictures on your slide in the upper right corner here as well as  as well as the lower portion here, we've got a heart wear device and a heart mate device in the  same patient and the users were able to simulate what might be the better fit for this individual  patient. So that is on the horizon. Also modifications that I've described here becoming  more standard. So you know these techniques for surgical implantation that promote circulatory  support are becoming more of the standard and as long as we publish and share our experiences  with that, we have opportunity to continue to improve. There's a need or desire to improve  wireless power so that patients no longer have a driveline. A driveline can be not only a tether  from a mobility standpoint but also an infection risk. And there's ongoing work of course to  improve the safety profile of these devices as they relate to stroke, bleeding, or infection.  There's ongoing work to share experiences and Action Network as well as PDMAX can be sources  for that. And then quality of life. Getting kids home is ultimately what we are looking to achieve  with progress in these devices and the approval of HeartMate 3 will facilitate that as well.  Thank you for your time and attention. I really appreciate it and enjoy the rest of your conference.  Good afternoon everybody. My name is Gideon Stitt. I'm a clinical pharmacy specialist in the PICU at Phoenix Children's Hospital and I'm excited to talk to everyone today about the  use of adult drugs for my pediatric patient and off-label use. Before we get started I have no  relevant financial relationships to disclose. And the objectives for this afternoon's talk are first to discuss the frequency of off-label medication use for pediatric patients.  It's a lot more common than I think a lot of people probably realize and so we'll actually  put some numbers to that fact. We'll then weigh the risks and benefits ascribed to off-label use.  So you know is this something that it's somebody going rogue or is it pretty normal practice and  how do we decide when to do that or not. And finally apply some principles of developmental  pharmacology to guide off-label medication dosing in pediatric patients especially for those more unique situations where we may not use things off-label as commonly.  Starting with the current FDA guidance when they look at the pediatric section of any package labeling there's really four scenarios that will guide what they list in  there. And the first is scenario one where the evidence supports the safety and effectiveness of a drug for an indication in pediatric patients. They've had well-designed studies  that have been submitted to the FDA and accepted and that dosing information is incorporated into  the package labeling. Scenario two is where the evidence does not support the safety and  effectiveness of a drug for a specific indication because they've looked at studies and they were  either negative or inconclusive and therefore just didn't support the inclusion of dosing  guidance for a specific indication in pediatrics. Scenario three is where there's no evidence  available to support safety and effectiveness of an indication in pediatric patients because  those studies either have not been conducted, they may be ongoing, or they may have been waived under  the PREA that's the Pediatric Research Equity Act which we'll discuss a little bit later.  And then finally scenario four that based on the available evidence the drug is contraindicated  for use in all pediatric patients. There's a clear reason to not use this drug in pediatric  patients and they're specifically calling that out. So with that in mind what then is off-label use?  Off-label use is generally defined as the use of a drug that is not included in the package insert  with FDA-approved labeling for that drug. It's basically the evidence required by law for label  inclusion either was not submitted or does not meet the regulatory standards of substantial evidence.  However, this doesn't mean that use is unsupported by clinical experience. There may be other data  in children, case reports, even relatively large studies that just didn't quite cross that line of  substantial evidence for the FDA. And it, you know, very importantly does not necessarily imply that  this use is improper, illegal, contraindicated, or investigational use. Simply that we're using a drug for any indication that is not specifically listed in the package insert.  And it's done very commonly and so there was a nice study done in 2015 where they looked at PICU patients specifically. They included just under 67,000 patients and of  those 67,000 patients 85% received at least one medication off-label with a median of three  medications off-label in that population. So this is very common in the ICU. They then looked at of  all the medications used in these patients which are the high use medications and they define that  as any drug that was used in more than 1% of their population. So of their 163 high use medications  over half, 84 of those, were prescribed off-label at least once and again within that high use  classification 46 or again more than 50% of them had no FDA approved indications in pediatrics at  all. And at the time of this study those included common medications like clonidine, dexamethamidine,  dopamine, a super old ICU drug, things like metronidazole, hydromorphone, and oxyparin. So drugs that we use all the time but weren't necessarily totally supported by what is in the  package labeling. So then the question is where are the data to support these indications? How are we  coming up with this stuff? And what it really comes down to is that you know many commonly  used medications lack pediatric FDA labeling. That's not always a problem. So a great example  are antimicrobials. It seems like most times that a fancy new antibiotic comes out it generally gets  approved for things like complicated UTIs, complicated intra-abdominal infections, and maybe  you know ventilator associated pneumonia, something like that. But we use antibiotics specifically for lots of indications that are different than those. However if we know you know  reasonably what drug concentrations we're able to achieve based on the volume of distribution of the  drug, what the safety profile of it is, it's very safe to use these medications off label when they  are easily extrapolatable in those senses. Also things like titratable drugs with relatively clear  efficacy and safety parameters. So things like vasoactives, sedatives, analgesics. While epinephrine  may not have dosing for pediatric septic shock in the package labeling, we have a lot of experience  using it for that and it's relatively easy to see whether or not it's working, whether your  patient needs more or less drug, and it's easy to monitor and adjust for those types of things.  Then we get the situation that I like to call black holes. So there are clinical situations  that may lack any published pediatric data at all. Things like extracorporeal membrane oxygenation  or ECMO and continuous renal replacement therapy or CRRT. And these are the ones that are a little  trickier. They tend to have much less sort of clinical experience, often little or no published  data even in case reports or case series. And so these are the ones where I think it takes a little  extra thought, where it's not a common off-label use, and so we have to be really careful about  how we're using medications in these situations. So Dr. Thibault and her colleagues at CHOP  published a great paper in 2019, where they looked at all the patients in their hospital who  were on ECMO and all of the drugs that they used, and then how many of those had any data at all  for their use in ECMO. And out of their top 10 drugs that were listed that had no pediatric  ECMO data published, you can see how common a lot of these are. And some of them, which we'll  talk about in our risk-benefit analysis, it's, you know, very reasonable and very safe to do so, but things like insulin, norepinephrine, docusate even, piperacillin, tazobac,  the very common drugs that we use in these situations that have zero published data for  them. So we have to think about those a little bit more carefully. Similarly, CRRT gives us some  additional challenges in the pediatric population. So oftentimes there's even scant adult literature  from which we can extrapolate, and that's where we pull a lot from in the pediatric ICU population.  Pediatric patients can have additionally altered protein binding relative to adult patients.  We have various filter membrane sizes in pediatric patients, and, you know, whether your patient is,  is, you know, a small infant or a 100 kilo teenager, generally speaking, they're all using  the same CRRT filters, but very different flow rates. It's that fourth one, variable CRRT effluent  rates, which can be very different than the adult literature. And so these all add up to, again,  really an additional level of challenge when thinking about how do I safely and effectively use a medication off-label in my pediatric patient.  And so I kind of walk myself through this risk-benefit analysis. Any time that I'm in  this situation where, you know, a simple off-label use of an antibiotic for let's say a soft tissue infection, that's not such a big deal.  If I've got good dosing and efficacy and safety data for other indications, but for, you know, these really unique things, you know, maybe in a patient who's on one  or even two extracorporeal circuit, I go through this analysis. I think, number one, do I have any alternative options? Anytime I can find something else  that will give me as good of efficacy, but I've actually got, you know, a little more data to lean on, that's always the most attractive option.  When I don't have that, then I think about what's the therapeutic index of my drug? So do I have a big, wide range of concentrations  where this patient will likely benefit from the drug with minimal toxicity? If I do tip over into that toxicity side, what is the toxicity profile?  So is it, you know, something like I've given them a little too much opioid and I've suppressed their respiratory drive, but they're already on a ventilator or on ECMO,  maybe they get something like an ileus or a common side effect, or is it something much more serious, like I'm gonna cause seizures or cardiac toxicity, for example?  So thinking about what is that toxicity profile and what is my tolerance for potentially crossing into that toxicity area just a little bit.  And then think about the developmental pharmacokinetics of the drug. So what is the volume of distribution for that drug? What about the volume of distribution of my patient  is different or maybe the same as other indications for what you may be used? And the same with clearance. And finally, therapeutic drug monitoring.  If it's a drug that I can monitor, even if it's a send-out, that's okay. We're getting to the point very quickly where you can get 24-hour turnaround on a lot of medications.  I'm a big proponent of therapeutic drug monitoring where you can. So that's sort of the last thing to think about, okay, I can think about my therapeutic index  and my developmental PK, maybe extrapolate from some adult literature or a case report in peds, and I've got an empiric dose, but I can also send some drug concentrations  and make sure that I'm getting it right. If I can run through sort of that analysis and come up with something that I feel good about, that I talk with my teammates with,  that this is how I've gotten to this recommendation, it's then still an appropriate situation to move forward with that drug.  So a couple of big things that really, I think anyone working in pediatrics, these are useful things to know about developmental pharmacology to think about what's different  about the patient in front of me versus maybe the patient that's in the package labeling or I'm extrapolating some dosing from. So the first is really the big thing  is change in volume and distribution. How big is the bucket that I'm trying to fill with drug to reach a target concentration? And I know that a newborn will have 80,  sometimes up to 90% total body water. And over time, that first year to five years or so of age, they're gonna lose a lot of that body water and be down more to 50 or 60%.  I always think about aminoglycosides as the perfect example. I want the same concentrations in adult versus a neonate, but I give a neonate sometimes twice  as much drug to get there.  What is the metabolism of this drug? So if it's something like 3A4, over 50% of drugs are touched by 3A4 at some point. You can see with the blue bars on this chart  that when you're born, you have very little 3A4 activity, which then rapidly picks up. So if I'm using something that's primarily metabolized by 3A4 and I've got dosing information  in let's say a teenager, but not a newborn, I probably need to give less because they're not gonna metabolize that drug very quickly.  And finally, think about renal function. How are they gonna clear this drug if it is really excreted?  Totally normal newborn kidneys often only have a GFR around 30. And so I probably can't extrapolate directly from, again, a teenager or an adult  where they might be getting something every six or eight hours. This newborn probably only needs it every 12, 18, or 24 hours.  So I know that these things are changing in these patients. And by knowing those details, I can sort of work backwards and think of how am I gonna dose a drug in this patient?  But at the end of the day, how do I do what's best for my patient? I walk through that risk benefit analysis. And once I've figured out, okay, what is my tolerance for toxicity?  How wide is my therapeutic index? I'm gonna use this drug. Are there any case reports or case series that I can pull from? If so, great, that can be a big, big help.  If not, are there adult data from which I can extrapolate and then use those developmental pharmacokinetic principles to work backwards? How do I utilize my network?  So we're not alone. The world is small and there are listeners, there is social media. Twitter is excellent for rapidly pulling your colleagues and getting some help.  And then colleagues from great meetings like SCCM, you can talk to and, hey, have you ever had a patient like this? Can you walk through this with me?  I bounce things off of teammates and colleagues all the time and that should really be encouraged. This is a team sport for sure. And then finally, I think what's really important  is proactively identifying objective efficacy and safety parameters and sticking to those. If I say, I'm not gonna use this drug if my white count drops below X, stop at that point  and we have to pivot and try something else because at the end of the day, you have to make sure that you're helping your patient and not harming.  So there's a couple of things that the FDA is doing to try to improve this. And it's been going on for 20 years or so. The first is the Best Pharmaceuticals for Children Act,  which is a voluntary process that encourages industry to perform pediatric studies to improve labeling for patented drugs used in children.  The sort of the carrot at the end of the stick is that companies can get an additional six months of patent exclusivity and it has allowed the NIH  to prioritize specific therapeutic areas and sponsor a number of clinical trials for off-patent drug products that need further study in children.  Very much related to this and I mentioned it earlier is the Pediatric Research Equity Act. And rather than where the Best Pharmaceuticals for Children Act is voluntary,  the Pediatric Research Equity Act is mandatory and it gives the FDA approval to require assessment of safety and effectiveness of a drug or biologic product used in children.  And they can do this either when the drug or biologic product is being used for a substantial number of pediatric patients for a labeled indication  and specific labeling could infer benefit so it could do it better. Or there's reason to believe that the drug or product that's being used  represents a meaningful benefit over existing therapies or the absence of labeling could pose a risk. So really when someone's looking to expand their drug labeling or a new drug,  the FDA will look at it and say, we either are or are not going to require pediatric studies on this drug for these reasons.  Overall, the BPCA and the PREA both been hugely successful. You can go on the FDA's website and see all of the labeling changes that have happened because of these two laws.  There's more than 850 labeling changes that have been enacted in response to these efforts. And overall, there's still lots of work to be done but between these legislative efforts  as well as sort of the thought process that I've tried to walk through in the last 15 minutes or so, you can see that off-label use can be very safe  and reasonable in pediatric patients.  So overall to conclude, off-label medication use is common in the treatment of pediatric patients.  It does not imply improper use of a medication but often does require some additional considerations and a risk benefit calculation should be considered  anytime a medication is being off-label. Finally, efforts continue to improve pediatric labeling and it's something that I really encourage everyone to proactively take a part in.  Just want to thank everyone for listening. I'd like to thank the Society of Critical Care Medicine for allowing me to do this talk as well as my colleagues on this panel.  Thank you very much. Hi, I'm Dr. Cameron S. William. I'm an adult and pediatric intensivist at Texas Children's and Baylor College of Medicine.  And I'm going to be drawing on that experience to talk to you about monitors and how they apply in adults versus pediatrics. I'd like to thank the organizers for this invitation.  I have no disclosures. Just to give you a quick overview of my talk, we're gonna start with reviewing some of the limitations and the accuracy of different forms of monitors.  And really, I wanna contrast adult and ped's critical care to point out where one or the other has an issue with the type of monitor. I'm gonna describe some of the principles  that actually underlie the monitoring because that's, I think, going to help with pointing out where it can be problematic in these different age groups.  And then finally, hopefully propose some solutions and recommendations that are based on evidence of what the best forms of monitoring are.  So in terms of the types of monitors, we're gonna start with what we all use routinely, and that's the ICU vitals, blood pressure, ECG, pulse ox.  We're gonna talk about hemodynamic monitors like cardiac output, fluid responsiveness, which depending on the type of unit you're in may be common or not.  And then finally, we're gonna leave off with ventilator flow sensors and some of the calculations done by the vet.  So to start with, telemetry is probably one of the most common forms of monitoring that we do. And I think beyond giving us heart rate information,  what's important here is, for many of us, is the ST segment measurements, particularly to look for elevation as a sign of ischemia or impending heart failure.  There's class 2A recommendations that ST monitoring be used for ACS and STEMI cases as well as open heart surgery, both in kids and adults.  Although the pediatric data is a little limited, there is data available showing that for congenital heart disease, Kawasaki's, the cardiac toxicity from different beta agonists,  asthma medications, and neonatal cocaine exposure, ST monitoring can actually be pretty helpful to point out when you have an issue.  I think one important difference is since children usually have supraventricular arrhythmias, using V2 as your lead where you're measuring arrhythmias  as opposed to V1 is what's recommended. And then finally, with kids, since the norms are quite different, it's important to set up profiles that are age appropriate for the child  and make sure you're entering in the age every time you have a new patient, so those follow. Let's switch to pulse oximetry. And I wanna talk a little bit about how pulse ox works.  The pulse ox is actually emitting two light wavelengths, one, which is red and absorbs primarily deoxyhemoglobin and the second being infrared, and that's primarily oxyhemoglobin.  And then since these are absorbed both in tissue as well as blood, the pulse ox has to separate this. So it uses the pulsatility that occurs with every beat  to take the arterial portion of the oxygen saturation and subtract out the stagnant or tissue portion. Likewise, it can separate out the desaturated blood.  Now, from this, you can see where there'd be some issues if you have a low cardiac output state because the lack of pulsatility is gonna make the pulse ox not be very accurate  for doing this subtraction. Second of all, if you have something like a failing Fontana with bad AV valve regurg and that's causing you to have significant venous fluctuations,  that's gonna throw off your pulse ox also since the oximeter is assuming that those fluctuations are primarily on the arterial side.  Nonetheless, pulse ox is pretty useful and accurate. You can see that there's almost no bias on average at about a plus or minus 5% range that the pulse ox operates in.  But this is mostly true when we're talking about higher oxygen saturations. So when we get to lower stats, for example, with kids with congenital heart disease,  you can see that in the range where a lot of our single ventricle kids are throughout their normal Glenn stages, you do have a little bit more bias and a lack of correlation.  And then if these kids are desaturated, the correlation actually becomes quite awful. And generally the pulse ox underestimates what the true arterial oxygen saturation is.  In adults, the situation that creates the most errors is actually diabetes. When you have a poorly controlled diabetic with a high hemoglobin A1C,  you tend to overestimate the pulse ox in those individuals.  Next, let's go to blood pressure. The non-invasive blood pressure cuff is something we all use in our ICUs, but it's important to note the very many different sizes  and it's critical to size it appropriately. So the cuff should be 80 to 100% of the arm circumference and about 40% of the length. And if you don't get that right,  you're either gonna over or underestimate the blood pressure based on whether it's too small or big.  If you look at how these blood pressure cuffs work, what they do is essentially a measurement through oscillometry. And so what they're doing is looking at the oscillations  within the blood pressure, oh, I'm sorry, within the blood vessel as the cuff is inflating. So when you get above the systolic pressure, essentially all the oscillations disappear.  And then as the cuff deflates, you start to develop some oscillations and those become maximal when the pressure outside, so namely from the cuff,  equals the average pressure inside the blood vessel. So at that point, you have zero transveral pressure and the largest oscillations occurring. So the cuff is looking for that  and that's how the cuff essentially assigns mean arterial pressure, which is really the most accurate value that the non-invasive blood pressure gets.  Then based on that, some calculations are done to come up with the systolic and diastolic based on some fraction of the mean pressure.  So right away, you can see based on using this calculation where some problems might be. If you have atherosclerotic disease where the vessel is stiffer  and the distribution of the systole and diastole or the pulse pressure is gonna be much wider than predicted, then you're gonna get false values from your non-invasive cuff.  Likewise, any changes in pulse pressure from things like vasodilation or constriction are also going to throw this off.  In general, blood pressure measured by a cuff versus arterial or aortic systolic is pretty accurate, but generally the cuff blood pressure  slightly overestimates your aortic diastolic blood pressure. And so as a result, you're gonna have a little bit of an underestimate on the pulse pressure.  Finally, if you're measuring radial versus femoral, I think in kids we use femoral more often just because of the size of the vessels. The blood pressure there  seems to be a little bit more accurate, whereas radial underestimates the pressure. And this is particularly relevant when you have a shocky patient on higher dose suppressors,  where you actually have a pretty sizable difference between the map at the radial femoral, five to 10 millimeters of mercury.  So if you're titrating off of a radial blood pressure cuff, you may be giving more pressure than you need to achieve the blood pressure.  Arterial lines also have other uses. It's important that you set them up right. First of all, a normal arterial waveform should have that nice dichroic notch  and not be too steep or too flat. If it's flattened out, it's over dampened and the systole and diastole are going to be falsely narrowed.  Underdamped art lines are much more kind of  peaky and dropping off quickly. And you can see these overdamping if you have bubbles or clots or kinks within your line, you're gonna get underdamping  if your tubing's particularly long or if the catheter size is large relative to the vessel. The impact that this is gonna have is primarily on things like non-invasive  cardiac output measurements that are using the arterial waveform. And also if you're titrating based on systole or diastole with your pressors,  then you may be falsely using a systolic value if it's too high or low, depending on what the situation is. Some of these things obviously you can fix  with moving the tubing or flushing the line. Others are a little tougher to deal with.  Finally, really important point is just to make sure you get your zero at the right place. If it's not at the heart, if it's under the heart,  you basically have a higher blood pressure than what's real. If it's higher than the heart, you are getting a low blood pressure. This is relevant, particularly in very active kids.  For cardiac output monitoring, this is a meta-analysis that looked at a number of different methods. And I think the key point is, is some of the devices that we use more often  in the adult world, like the pulse contour waveforms, like FloTrack and Litco, aren't particularly good in kids. Where the best data is, is actually in electrical cardiometry.  And I'm gonna talk about that in a second. And second best is ultrasound dilution. I think both of these techniques are actually less commonly used than the pulse contour analysis.  And for that reason, I'm gonna review both of them. It's also important to note that ultrasound blood flow,  like the OSCOM, is actually kind of bad and probably not useful in pediatrics.  So electrical cardiometry is based on the principle of bioimpedance. And what's happening there, is that as the blood is being pumped and the blood cells line up,  they have an electrical impedance that actually goes with that alignment. And so similar to the arterial upstroke, which can be used to estimate cardiac output,  this change in impedance can also be used to estimate cardiac output. It's more rapid if you have good cardiac output and less in low cardiac output.  An example of this device is the ICOM device. And this is a picture from a paper that used it showing how the monitor leads are supposed to be set up.  A very similar technology that's used in adults, but not really tested so well in kids, is the NICOM device, which uses the principle of bioreactives.  Both of these give you pretty good non-invasive cardiac output measurements in the respective patient populations. Ultrasound dilution is a technique  that is useful even in neonates. And in this situation, you're taking advantage of the fact that ultrasound velocity of blood decreases when you add saline.  So here's the ultrasound velocity of blood, here's that of saline. And what happens is blood is being removed from the arterial line. A sensor is measuring the velocity.  Then as it passes through the pump on the venous end, you actually introduce some saline into it and then inject it into the patient. And so the time that it takes  to then circulate back around to here and what the dilution is, allows the device to come up with a cardiac output measurement. What you can see in this study  is that as the children got older in terms of gestational age, their cardiac output, which is a small dot, went up as one would expect. Whereas their index,  which is already normalized to their size, stayed pretty flat, which again is what one would expect and shows that this is a fairly accurate method even in neonates.  Fluid responsiveness is important particularly for resuscitation. This is essentially understanding whether somebody will have a bump  in their cardiac output if you give them a bolus. And in adults, we often use the pulse pressure variability on the arterial line since most of our shocky patients have one in.  And there we're looking during mechanical ventilation at how much change occurs in the peak pulse pressure versus the minimum pulse pressure.  And that gives us a pulse pressure variability as a percentage. If that percent is above 13%, a variety of studies have shown that that goes with fluid responsiveness.  And really what this is telling you is that the swings in intrathoracic pressure from the ventilator are causing significant preload changes in the heart.  And that if you load that heart further with volume, you'll get a bump in the cardiac output. Now in children, this method has actually been pretty poor in terms of its reliability.  And I think there's a couple of reasons for that. One is that in kids, their compliance with their chest wall is much better. So the pressure from the vent,  a little less of it actually impacts the heart and the blood vessels to cause as much stroke volume variability. And the next thing is that your vessels are more compliant.  So to some extent, they have less of the fluctuations than one would expect from the changes in chest wall pressure.  What's more promising is actually the change in the peak velocity measured at the aortic valve, which is what we're gonna look at in the next slide. So this is a meta-analysis.  And in this meta-analysis, you can see that the change in the peak aortic velocity actually has the best prediction of fluid responsiveness,  in some cases in the 0.9 range and higher. Second to that is the use of passive leg raise, which is essentially if you have a non-invasive cardiac output monitor on your child  and you lift up the legs, you see if there's a bump in the cardiac output with that maneuver.  The aortic peak velocity change is essentially one where you stick your cursor with a pulse wave doppler on the aortic valve or the outflow track, and you're looking at the change  between maximal and minimal velocity. The equation for that is right here. And basically based on how much of a change you have, you predict whether or not you have  this stroke volume variability, which implies fluid responsiveness. The nice thing about this is now you've removed those other factors, namely the vascular tone and compliance  and the intrathoracic compliance, which I talked about as making pulse pressure variability  not so accurate, because here you're looking directly at the heart, which is probably why it is so accurate.  Finally, I want to conclude with some of the flow sensors we use. So routinely we use ventilators where the flow sensor is on the vent or in the vent,  but in children, there's some significant advantages of putting the flow sensor proximal right by the child. One of the benefits is pretty obvious, sensitivity.  So if you're using invasive ventilation or non-invasive in particular, the child can better trigger that ventilator because the flow sensor is close to them.  The only downside that I've encountered with this is that when you have a proximate flow sensor, if you're using nebulized treatments or there's a lot of condensation in the tubing,  that's basically going to get into the sensor and throw off the measurements. And you're going to have to routinely take these out, dry them out, put a fresh one in.  But if your RTs are on top of it, it works just fine. The other thing that's important about flow sensors is that the machine is using them to make a calculation  on how much volume is being lost due to tubing compliance. So every time the vent fires, the tube stretches out and that stretch is essentially lost volume,  which the ventilator tries to account for by taking the circuit compliance and putting it in this equation to compensate. The problem is, is you calculate  the circuit compliance early on. And then if things change like the patient's resistance or if there's some leak, this changes, but you're not actually remeasuring it.  So this ends up being a pretty faulty assumption.  The fix for that is to put the actual flow sensor right up against the tube. And as you can see in this example, the differences can be substantial.  So let's look at children who are breathing in the range of 80 to 120 mLs. At least that's what the vent thinks it's delivering. What we see when we put a flow sensor here  proximal to the ET tube is that in fact, what they're getting is about 35 to 80 CCs. So substantially lower tidal volumes than one would expect.  The changes, as I mentioned in tidal volume, actually change with compliance and resistance. So the children with the lowest compliance  and the highest resistance are actually the ones who are gonna experience the biggest differences. So really what we're saying is that your sickest kids  are gonna be most impacted by this,  which is more reason to wanna get that proximal flow sensor. So just to summarize,  there's a lot of monitors that we use in adults, but only a fraction of them have been validated in kids and proven useful. There's some important limitations that exist  for all monitoring, particularly in diseased patients. And those are true between adults and kids. But I think some of the more promising pediatric methods  are the use of aortic peak velocity for predicting fluid responsiveness and proximal flow sensors on the vent when you're using invasive or non-invasive ventilation.  So I'll conclude there. Thank you for your attention. ♪♪♪

Video Summary

In this session, the moderator and speakers discuss the intersection of adult and pediatric care in the context of ventricular assist devices, drug use, and monitoring in both populations. The first speaker discusses the limitations of using adult ventricular assist devices in pediatric patients. She highlights the differences in technology between adult and pediatric devices, as well as the challenges in bringing pediatric devices to market. However, she also mentions some recent approvals and developments in this area. The second speaker talks about the use of adult drugs for pediatric patients, specifically focusing on the off-label use of medications. She emphasizes the frequency of off-label medication use in pediatric patients and discusses the risks and benefits associated with this practice. The third speaker discusses the differences in monitoring between adults and pediatrics. She covers various types of monitors such as telemetry, pulse oximetry, blood pressure, and hemodynamic monitors. She also mentions the importance of setting up monitors correctly and highlights the limitations and accuracy of different monitoring methods. Overall, the session provides insights into the challenges and considerations when treating pediatric patients in the context of adult care.

Asset Subtitle

Pediatrics, Procedures, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Learning Objectives

Discuss the frequent off-label use of medications for pediatric patients and the risks and benefits ascribed to off-label use
Identify the limitations of applying adult-based technology for heart failure, including ventricular assist devices, to pediatric patients
Review the limitations of monitoring technology for pediatric patients compared to adult patients

Adult Ventricular Assist Devices for Pediatric Patients
Aimee C. Jennings

Adult Drugs for My Pediatric Patient: Off-Label Use
Gideon Stitt

This Monitor Doesn't Fit My Little Patient
Cameron Dezfulian

Meta Tag

Content Type Presentation

Knowledge Area Pediatrics

Knowledge Area Procedures

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Monitoring

Year 2021

Keywords

ventricular assist devices

drug use

monitoring

technology

off-label use

medications

approvals

developments

monitor types

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