SCCM Resource Library-Squeezing the Beans: Critical Care Nephrology

Video Transcription

I want to take the time to welcome you to this session on Squeezing the Beans, Pediatric Critical Care Nephrology, and I want to thank you for taking the time to join us.  Today during this session on Squeezing the Beans, we're going to be discussing the impact of fluid, how it impacts our patients in the ICU, both under and over fluid overload,  how do we treat fluid, how do we give fluid, what's the appropriate time. We're then going to shift into talking about AKI biomarkers. What is the present state?  Are they ready for prime time? How do we use them? What can we do at the bedside? And how do we shift them from translational to bedside?  Then we're going to wrap this session up with discussing renal replacement therapies and how we provide and select therapies for AKI, what's the appropriate therapy, and we're  also going to end with highlighting what's new and exciting in pediatric renal replacement therapies.  I also want to take this time to introduce Dr. Barhart, who is a pediatric intensivist at Ann and Lurie Children's Hospital in Chicago as well as Dr. Basu, a pediatric intensivist  at the Children's Hospital of Atlanta. Hi. Thank you for inviting me. My name is Matthew Barhart.  I'm an assistant professor at Lurie Children's Hospital and I get to talk to you guys a little bit about impact of over and under hydration on outcomes in the pediatric ICU.  I have no financial disclosures to report. Shock and respiratory failure are very common in the pediatric ICU.  It is our primary objective as intensivists to reverse this shock and to save the lives of our children.  Patients need fluid resuscitation and oftentimes they need large volumes of that resuscitation.  This fluid will restore venous return, it restores the preload, it augments our cardiac output, and it will improve the perfusion to all of the end organs that we need.  This is our main job as intensivists. We reverse shock. We understand fluids are life-saving therapies. However, excess fluid balance is harmful.  We understand that the detrimental effects of fluid are just as well known. Fluids build up in our organs. This excess fluid can impair oxygenation.  It can worsen our lung compliance. It can lead to venous congestion that will impede perfusion and the data is very clear that excess fluid is harmful.  There are meta-analyses that have come out a couple years ago that demonstrated that a critically ill children by definitions either of fluid balance or by changes in their weight  are harmed by excess fluid. Furthermore, a few months ago there was a meta-analysis published in critically ill adults that demonstrated the same harmful impact of fluid overload.  Now this is a difficult tightrope to walk and how we balance between life-saving therapies and iatrogenic harm is not simple. And so what do we do with these data?  Well, here's what we say we do. This is a survey that came out a couple of years ago of intensivists who were asked about  their practices regarding fluid management in the pediatric ICU, particularly related to pediatric ARDS.  And what they found is that the large majority agreed that conservative fluid management is beneficial for our patients.  Interestingly, more than two-thirds reported starting maintenance fluids at at least two-thirds  of a maintenance rate or greater, many of which were considered full maintenance fluids. So the method that they used overwhelmingly, 96%, was the 4-2-1 method for maintenance  rate calculations. For those of you who are less familiar with the Holiday Seeger 4-2-1 method, this is where You use 4 mLs per kilo for the first 10 kilos of the patient's weight.  You use 2 mLs per kilo for the second 10 kilos. And you use 1 mL per kilo for each additional kilo beyond those first 20 kilos.  Furthermore, the majority of the intensivists suggested that we should be acting on some degree of around 10% fluid overload or more as a threshold.  Now what acting on was different depending on the responders. Some felt that we needed to limit fluids in. Some meant that we needed to focus on diuresis.  But I want you to keep this number in mind of 10%. So let's have a little fun with math and look at what happens for a patient in what 4-2-1  means in a 10-kilogram kid for the first three days that they would be in an ICU. Well 4-2-1 for 10 kilos equals 40 mLs per hour. 40 mLs per hour is 960 mLs per day.  If we assume that they have a pretty reasonable urine output of 2 mLs per kilo per hour, that would be 20 mLs per hour and 480 mLs per day of urine output.  They would have a net fluid balance of 480 mLs per day. If we calculate the fluid overload percentage based off of those changes, after one day we have about 5% fluid overload.  After two days it's 10% fluid overload and after three days we have 15% fluid overload. 15% fluid overload. That is an enormous amount of fluid.  As we just said, we felt that as pediatric intensivists we should be acting on 10%. We are causing that as we give a large amount of this maintenance fluid.  I want you to also think about some of the assumptions that were made here. This patient doesn't have oliguria or anuria.  2 mLs per kilo per hour of urine output is better than many of the patients that come through the pediatric ICU.  None of this takes into account any other fluids that a patient may have received. This is not including resuscitation fluid.  Any fluids are given for antibiotics, sedation drips, vasoactive drugs, blood products. This is just maintenance fluids. This is a significant burden.  Why are we even considering waiting on this and waiting until we've created it when we could potentially prevent it?  Now you may say, well this is fun, that's a hypothetical, that's not really what would probably happen in real life. Well so let's look at what the clinical data really tells us.  60% of the total fluid administered for the first week of fluids in an adult ICU was either in the form of maintenance fluids or fluid creep.  Now they defined fluid creep as those medications, the fluids for keeping veins open, carriers for other medications, those sorts of things.  In septic adults they tried to model the amount of fluid that we would have and if you potentially changed to have a fluid restrictive mechanism.  Could you reduce fluids given to patients? In this way, if they limited the amount of maintenance through a maintenance restriction,  you had a potential reduction of almost three liters in the first couple of days for these septic adults. How about in the ICPQ?  Well a study recently showed that 65% of the total fluid given in the first day of the ICU was modifiable and they defined that as things like maintenance fluids and certain  medications not including resuscitation fluids and those sorts of necessary absolutely needed fluids. That number only dropped to 46% on the third day in the ICU.  Maintenance fluids account for almost half of the total fluid in day one, 43% in day two, and 26% in day three in a different study for critically ill children.  And then we have a study that's under review currently and what we evaluated was the non-resuscitation  fluids that were given to our patients and specifically the amount that was given in excess of that 4-2-1 calculation and we found that more than half of all PICU admissions  had fluid that was non-resuscitation fluid that was in excess of 4-2-1. And among the patients that had greater than 20% fluid overload, 92% of those received  fluid in excess of 4-2-1. So why do we have this discrepancy in what we mean to do and what we are actually doing? Well it's fairly simple, it's our culture.  Our culture is such that we have learned since the beginning of pediatric residency how to calculate maintenance fluids.  I think it's the third thing you learn after albuterol is helpful for asthma and vaccine saves lives.  We learned to calculate maintenance fluids and we start it on all of our patients. I want you to think about as you listen to me our current practices in your ICU and I'll  think about it in mine because these are important questions.  If we make a patient NPO for whatever reason, how often do you start maintenance fluids?  Do we ask ourselves whether this patient needs maintenance fluids or do we do it reflexively? Do the residents or the advanced practice providers just start it because the patient  was made NPO? Do we consider the other volumes of fluid that the patient receives? Do we use a total fluid order to limit the amount of maintenance fluids that is given?  Do we consider their insensible losses? Are we going to consider whether they have fevers? And if they have fevers they're going to have an increase in their insensible losses.  Maybe they need more fluid than what we would initially write for. Do we consider whether they have humidified air because they're ventilated and we should  restrict the amount that they have? Or do we just give the volume that the 4-2-1 calculation spits out?  The last question is when we start enteral feeding, do you stop maintenance fluids? Do you decrease the maintenance fluids?  Or do you just wait until the enteral feeds are at goal and then you turn them off at that point?  Fluids are medications and deserve the same thought and the same consideration as all other medications that we are giving them.  There is a joke in the IT world where the IT support man will get on the phone and talk to a customer and then as he gets off the other IT person will say to him, how was that call?  And they'll respond, oh it was a picnic. Well picnic stands for problem in chair, not in computer. Now we often blame our outcomes on the patient and their patient-specific factors.  We will say things like the severity of illness is high, therefore these associations with fluid are just due to the patient.  Well I have a different question that I want to ask you. Are we in that same idea of problem in the computer, not in the chair, are we the ones causing the problem?  Are we the ones who are the problem is in our culture and not in the child? Because we owe it to our patients to ask ourselves what role do we play in developing these outcomes?  Specifically the things that we do on autopilot. The systematic care that we provide. And this is not just maintenance fluids.  I'm harping on maintenance fluids because I think that that is a significant burden that we need to address in our culture. But it's not just that.  It's also about the way that we fluid resuscitate. Do we frequently evaluate fluid responsiveness?  I was recently on service and I performed a passive leg raise and my team looked at me like I was performing some sort of magic act.  That is a failure on my part in educating my fellows, our residents, and our APNs so that they can realize that these are things that we should be doing.  How about our awareness of fluid overload and AKI? Well, in one of the studies that we had mentioned before, in patients that had greater than  15% fluid overload, the team lacked recognition of that fluid overload in 30% of those patients.  In a different study, it was a survey to evaluate how well the PICU providers were using current  AKI guidelines and 46% of the patients weren't regularly using the current AKI guidelines. How about diuresis?  One study showed that a fluid bundle could lead to lower percent fluid overload in the first few days, 6% versus 12%. They had earlier extubations and a shorter length of stay.  In a different study, they implemented a diuretic protocol and that diuretic protocol led to improved diuresis.  In fact, it actually had a negative 2 liters of fluid out in the first few days compared to a positive 0.3 liters in the standard of care.  There were higher ICU free days and they even had a lower mortality. Now, cultural impacts on care are not new and we have been here before.  Enzodiazepines used to be ubiquitous for sedation. Pain control used to be with continuous opiate drips and not with PCAs.  We have learned from our mistakes and we have guided our therapies accordingly. So in conclusion, I want to leave you with a couple of thoughts.  First is we need to reevaluate our cultural assumptions. We need to change the way we use our maintenance fluids and we need to raise awareness about  kidney injury and fluid overload. Maybe we can even get a way to predict which patients are likely to become fluid overloaded.  We need to reconsider how we de-resuscitate because to the question of why we do something, the answer of well we do it that way because we've always done it that way is just not  a good enough answer. Thank you. I will be happy to answer any questions at the end of this session during the live Q&A.  Good afternoon, everyone. I'm grateful to have this opportunity. I appreciate the Congress's invitation to give you this talk on biomarkers.  We're going to talk about potential versus reality or fact versus fiction. A couple minor disclosures to kind of tell you about, but the major one is really that  in this whole field of biomarker diagnostics and AKI, the biggest thing we have to remember is that we can make a difference.  There's so many people walking around because of the associations of AKI who say it is what it is. We can't really do anything.  Well, I'm not one of them, nor is Theresa Mottis, nor is Matt Barheit, nor are many of you in this room who are listening to this talk.  So let us get past that and say that nihilism is to be overcome. We can make a difference and biomarkers may be one of those ways.  You're listening to this because you believe in the following, that AKI is an important disease process.  These are probably the biggest articles in the past five years to discover the epidemiology of AKI across critically ill populations, ranging from birth to geriatric populations.  What we have found is remarkably consistent. Independent of severity of illness, independent of age, independent of where you are, AKI is associated with death and worse outcome.  One in four critically ill patients has some form of AKI, and there's a dose response. The worse your AKI is, the worse your outcome is.  We know that it's not just the people who die. The people who survive have a worse quality of life.  We have data from children and from the adult color cohorts that tell us that AKI is associated with worse outcome.  So it doesn't matter what stage of life you're in, AKI makes things worse. We also know that it's associated with increased healthcare costs.  This is Canadian data that shows admission through time of inpatient, through time of discharge associated with significant costs for AKI.  U.S. data tells us there's over $10 billion per year spent specifically on AKI management. Length of stay increases even if you're not in the ICU, and overall expenditures go up.  So the question is why? Why would it be this way? We have to ask if whether our poor outcomes are driven by management alone, or perhaps  because we're just not doing a good job recognizing the disease process. So let me give an example of what would be a corollary in a different field.  Imagine that you're not an oncologist, but you tell an oncologist, I'm taking care of this patient. The patient has a white blood cell count of 34,000. So he has cancer.  And I know what type of cancer, I know what to do, how bad it is, how long it will last, how long the recovery will be. Would that be acceptable to you? I don't think so.  I don't think it'd be acceptable to the oncologist either. So for many years, what we've said is can better diagnostics help us move the needle at all?  Can we do better than what we're doing? And the reason is this. If you track AKI diagnostics through the decades, we've had this remarkable journey of progress.  We know that there's this marker that tells us everything we need to know about AKI, where it's happening, what type of AKI it is, what the etiology is, how severe it'll be.  And we've really made progress, right? Well, the truth is we need to do better than this. And biomarkers for AKI have apparently been the answer, or are they?  This time we deal with the fact and the fiction of biomarkers for AKI. So I'd like to draw this parallel between biomarkers and a mentor, something that all  of us probably can relate to, and what they are. A biomarker is an objectively measured indicator of something that happens. It's a pathogenic process marker.  It's usually noninvasive, easy to get, easy to measure, is quick. Just like a mentor, something that's objective, easy to interact with, remarkably reliable  and quick, and doesn't cost you too much pain or suffering to deal with. What we want them to be, however, is a crystal ball, a Nostradamus of sorts, a jack-of-all-trades  that tell us everything and anything that we need to know. Well, that's not true. And what that leads to is this disconnect of expectations and reality. It does not work that way.  So what we need to figure out is what is the reality for biomarkers for AKI? For years and years, just like at SCCM, when we'd have plenaries about whether cuffed  or uncuffed tubes are better for mechanical ventilation, if you go to any big nephrology meeting, one of the big plenaries was, were biomarkers ready for use at bedside?  Were they ready for prime time? And the question ended up being, is it all the time? Is it the time when I need them? Is it any time? Is it results in real time?  Well, the question for that is, well, those are all focused on me. They're all focused on you.  They're not really focused on the patient, because what we should be thinking about is, can biomarkers help us understand the disease process? What about the patient?  So if we map this out, several authors who are really remarkable in AKI biomarker world have discussed this idea of what the promise is, because we discuss, okay, here's an example.  Here's a marker that we call NGAL, a tubular damage biomarker. There's this idea that there's this window of opportunity there where you can diagnose  AKI early, earlier than changes in creatinine, and because we can do that, it gives this idea to do that early intervention. It gives us an opportunity to make a difference.  The reality of this situation is once we started measuring some of these things at bedside, it was not that linear. It was not that clean. It was super noisy.  And part of it is that we didn't really know, okay, is there an opportunity for early intervention? Because nothing was consistent.  If you look back over the last 10 years, even the last 15 years, there have been a lot of biomarkers that have been studied.  This paper is actually 12 years old now, or 13 years old, and it talks about over 30 biomarkers used for AKI for differential diagnosis, detection, prognosis.  When you put all the data, if you were to get a meta-analysis and say, I need to find out which one to use and how to use it, this is what it looks like.  It's a mishmash of tables and AUC values and what to do, and it doesn't really tell you all that much.  It's pretty confusing as it relates to the patient and the marker itself, because what we need to ask ourselves is, are we working toward actionable information?  Are we looking at data that's population-driven or patient-driven? Can we study cohorts or individuals?  The biomarkers that we study, they're using cut points, but those are for area under the operating or area under the curve receiver operating characteristics.  Sensitivity, specificity doesn't really tell us what to do. They're all about AKI diagnosis, and what ends up happening when you have all these  things that are, quote, competing with each other, is you get a war, and this picture is drawn from the Pearl Harbor radio operators, the origin, an AUC ROC term, people that were  trying to delineate whether pings were bombers or just birds or seagulls, and so we need to think about this reality of, well, what are the purpose and what are the data that  we're looking at? What is the purpose? I put this together about a year and a half ago, and this was a map at the time, a planetary  map of all the different major one biomarkers that have been published, and as you can see, there are thousands of publications, lots in adults, lots in pets, lots in neonates,  lots in cross populations. Do they tell us more than just this patient is related to AKI? Well, here's the thing.  The biomarkers that we have can tell us a lot about when the initiation, when the extension  of injury, when the maintenance and repair, when the injury may extend into chronic disease. The biomarkers can tell us where an injury is happening, proximal tubule, distal tubule,  in the nephron, in the glomerulus. It's different for each biomarker, and it's not simply okay to say the creatinine's up so the patient has AKI.  That is the equivalent of saying, well, your troponin is one, so you have heart injury or heart failure. A cardiologist would never accept that.  NGAL is a good example. NGAL is a ubiquitously expressed protein, and it goes up in times of stress. It's increased translation in sepsis. Here are the early data for NGAL.  It's higher expressed in the urine than creatinine ends up being, but it is not a perfect biomarker on its own. It tells you that there's tubular damage going on in the kidney.  We could also have biomarkers that tell you a mechanism of injury. Here's a cell cycle arrest marker that tells you when tubular epithelia are put into a  phase of cell quiescence because they're under stress. The example of that is the TMP2-IGF-BP7 marker, also known as nephrocheck. These things tell you different markers.  This is a good summary paper about how nephrocheck or TMP2-IGF-BP7 is integrated into a management paradigm, which brings up this idea of, well, can we use them in a real way?  One biomarker many of us probably never even consider is the response to diuretics. But if you think about it, when you give a patient diuretics, when you give someone furosemide,  you rely on furosemide going into the luminal side of the renal tubule, getting transported to the leukopenly, acting at the chloride transporter, and inducing a diuretic response.  That requires a lot of tubular function. When you quantify urine response in response to a dose of LASIK, and this is called the  furosemide stress test, you get a much greater sensitivity and specificity, excuse me, for  the development of AKI, for the progression to renal replacement therapy, for the prediction of death. It is a functional marker. And guess what?  It's something we all do and we all use. So there are other things we can use to tell us about the kidney. We can also use machine learning tactics to develop risk scores for AKI.  So many more people are doing this to leverage the EMR to tell us data on admission, whether it's related to vital signs, lab function, or whatever, to develop renal AKI or the use  of KRT or kidney replacement therapy within the next 48 hours in this table in our patients who are admitted. So can you use them, right?  If we have these abilities, can you actually use them? What could you do if you had a biomarker? Well, here's a good example of what you should not do, which is test everyone.  One of the things we know is that our current markers tell us when GFR goes down. And what we think we need is the biomarkers that tell us about damage before the GFR goes down.  So in this linear spectrum of pink kidney to black kidney, we'd like it to be somewhere  in that dusky-looking, pink to kind of purplish, but not yet in that GFR-decreased gray-purple. Furthermore, we'd love it to tell us, well, you can target who you're testing.  Because the best way to ruin a test is to test it on everyone, because that doesn't make any sense.  So there are a number of prediction algorithms or context-driven prodromes that are out there now that can help us identify the cohort of patients that are at highest risk or at the  lowest risk. We developed one called the Renal Angina Index, which is quite simply a marriage between risk factors and early signs of injury.  And what it does is it directs you to which patients actually would benefit from getting a confirmatory biomarker test.  When we put it to the metal in over thousands of patients now, what we find is if you test  this Renal Angina Index prodrome on the day of ICU admission, it's got a very high negative predictive value for day three severe AKI, which is important since those patients who  survive who you're even testing this on are pretty sick. You'd like to know, do you have the wiggle room for fluids, nephrotoxins, food, blood, whatever it is.  So if you have a high negative predictor, that's very helpful. We also know it's got a reasonable sensitivity and specificity, much better than any severity of illness.  But what it really does is it helps us direct our biomarker testing, just like what we do when we have a patient who has acute coronary syndrome.  We never knew what to do until we married the Framingham risk factors with the person who's got chest pain and other symptoms to direct us to EKG troponin testing.  When we do this in our patients, we figured out that Renal Angina Index guided testing has a unity score of near one for prediction of severe AKI.  So if you're interested, this is on Wikipedia. It's there. It's where I put it, so it should work there. You could also do this management guideline.  So many people may not know that AKI management guidelines actually exist. So this is an adult-based KDGO guideline, the Kidney Diseases Improving Global Outcomes.  It's soon to be revised. But the management steps aren't all that remarkable. But maybe the biggest one might be discontinue all nephrotoxic agents.  How do you know when to use them? Because putting this to the test in all 50, 60, 70 patients in your unit may be a little cumbersome.  What if you had a way to kind of stratify patients? Well, there were a series of studies done in Germany looking at randomizing high-risk surgical patients by a biomarker test.  In this case, they did the nephrocheck test. This data comes out of cardiac surgery. Patients who came out of cardiopulmonary bypass were given this biomarker test.  And then the patients who had an elevated biomarker were randomized into that bundled care of that guideline approach versus standard of care. And guess what they found?  Just by doing what we think we can do with conscientious management, you reduce severe AKI and moderate AKI, but all cause AKI just by incorporating a risk-stratified approach.  Engel also, just like the other biomarkers, has a approach to this cardiac surgery score, giving you a sense of what can you do based on the tier of elevation.  And here's an example of a map that tells you how to target venous oxygen saturation,  where a patient should go, who should be involved. The ADQI workgroup said, why don't we refine our AKI diagnosis?  So instead of saying pre-renal, ATN, maybe you have a combination marker, a functional damage-associated AKI.  We did this, and we found that when you combine a damage marker and a functional marker, you can predict the patients who actually just have a postoperative increase of creatinine  without actually true AKI. This is remarkable, because it tells you you can predict AKI earlier, but also tells  you severity, duration, or versatility, something you couldn't have done with just creatinine.  The ADQI group has recently come out with initiative and recommendations for biomarkers, and what they tell you is we should be using them to phenotype AKI, target management,  and use context to direct testing. Here's a good example. That two-by-two box I just showed you, it incorporates biomarkers, such that what's  coming is that a new diagnostic stratification of AKI, where we not only use creatinine in your urine output, but we have biomarker, biomarker, negative, positive, and negative  to tell a subclinical and actual AKI. So this is what's coming to you. This is what's going to happen in the sense of refining AKI diagnostics.  So the promise of biomarkers for AKI, they come in multiple forms, should be studied dynamically over time, just like a blood gas would be. You can delineate the phenotype of AKI.  You can help refine AKI that requires urine replacement therapy. Could you personalize your management? This is a potential schema for that.  You take a bunch of patients, you can delineate them into patients who are high-risk or low-risk  for fluid, and then use more biomarker testing to tell you who actually has urine replacement therapy needs, who has functional AKI.  This is really what we should be able to do, and what they did in cancer, in cardiology, in years and years and decades ago. Here's a good example.  We have a blood gas for use in respiratory failure. We could do the exact same for AKI. Combination of homeostasis, solute transfer, reserve, compensation, tubular function, system  stress. These are possible to do. So the fact versus fiction is really this. We had hoped that biomarkers would turn a moron into a less of a moron. That's not really true.  What we need biomarkers to help us with is to turn somebody who's already thoughtful into somebody more informed, because the past is very black and white and is probably associated  with a lot of poor outcome, an epidemic driven by the fact that we just treated everyone the same. One size fits all.  But the future is much more colorful, much more dynamic, much more context-driven, and much more refined and personalized for the patient. It's not just science fiction.  It's not science fiction. It's just science. This is where we're going with our testing. With that, I'll stop. And I appreciate the opportunity to give you this talk.  Thank you very much. I want to thank Dr. Barhart and Dr. Bizzou for their great presentations prior to this wrapping up of the session, now looking at renal replacement therapies.  They adequately set me up to talk about what's old, what's new, and everything in between. These are my disclosures for this talk. They do not have any relevance.  I will not be speaking specifically to machineries or therapies. So renal replacement therapy has been around for decades.  It was introduced in the late 60s and 70s, but in the AKI world really took front stage in the mid to late 80s.  And it was started because the traditional therapies here of HD and PD didn't completely fit the patient population that they were caring for.  So they started thinking about what other modalities can we use to fit a specific patient population.  And as a result, a multitude of modalities and therapies have been introduced in the last two or three decades to serve this patient population.  Traditionally HD in its intermittent state did not serve the AKI critical care nephrology population.  And now we have many therapies that we can think about and use to introduce into our patients.  But with multiple modality selection, we have to think about what is the right therapy. How do we select a therapy that matches our patient's needs?  And in 2012, as you can see, Kate Eagle, which we're all very familiar with, published the AKI guidelines, sort of gave us some guidance as to what patient population may benefit  from an intermittent therapy versus a continuous therapy versus an in-between type therapy. So we need to think about how do we want to fit that into our patient population.  And ideally, when we're talking about selection modality, it's really balancing what the therapy goals are with our patient characteristics. Is there a need for fluid removal?  What kind of solute control? Is there a specific target molecular molecule that we are targeting that may benefit from one selection modality versus the other?  And ultimately, what does our patient look like? What are the disease burden and patient complexity?  Product stability plays a huge role in what we decide as far as modality, the fluid status, and ultimately, how do we provide what our patient needs on an hour and day-to-day basis  to ensure that they are getting what they need and balancing that with our renal replacement therapy? Are they getting adequate nutrition? What are the medication requirements?  What is the blood transfusion burden? All of those should be playing a role in how we decide selection modality.  With that said, we then have to think about what are the selection modalities, and I'm specifically at this point talking about a continuous renal replacement therapy, although  it does apply to some of the intermittent. If we've balanced what our therapy goals are with what our patient characteristics are,  we need to think about providing a modality that is diffusion versus convection, and is there a benefit to one or the other?  You can see here in this systematic review by Dr. Friedrich that was published in 2012 looking at basically all the literature around renal replacement therapies and compiling  that data and looking at diffusion versus convection in a specific molecular size clearance.  You can see that if you're targeting a higher molecular size molecule, convective is superior to diffusion.  It's important to remember that your small molecules, there's no difference between clearances. One is not better than the other.  Of course, this was adult data, and Dr. Ricci, pediatric intensivist, published their data in 2006 finding very similar results that convective therapies is superior to higher  molecular size therapies to a cutoff. The next thing we think about is if we're targeting a continuous therapy, is diffusion or convection going to prolong our filter life?  Again, in this systematic review looking at specifically filter lifespan, was convection versus diffusion superior?  Ultimately, it looks like, according to this systematic review, that hemofiltration, so convective type therapies, is associated with a shorter life.  That held true in the systematic review for pre- or post-convection. If all things are equal and you are not targeting a specific molecular size molecule, probably  a diffusion-based therapy selection is superior when it comes to filter life. The final thing we really need to think about when we're thinking about looking at a selection  modality is the mortality. Again, looking specifically at this very detailed systematic review from 2012, there is no effect  on mortality, renal replacement dependence, or vasopressor use when using diffusion versus convection.  If all things are equal, again, there's no superiority in one versus the other. This data remains controversial and is still being studied, and we will see what the future  holds for how does convection versus diffusion play out, but ultimately, renal replacement  therapy modality selection, diffusion versus convection, ultimately sort of lies with where you currently practice.  If you're in Europe versus the United States, there's some selection criteria that will change based on where you're at.  In the absence of real clear evidence, modality selection in general is provider-specific or institution preference.  Mod is available at the institution rather than looking specifically at patient and objective outcome data. With that said, what's new?  We're starting to see emerging in the literature this in-between modalities. This was a study published by Dr. Menon and colleagues looking at three centers, looking  at using a non-CRRT machine to provide therapy for a unique patient population. You can see on the left that this was data that was published in 2006 looking at the  survivability of the smallest patient population that we deal with. See that under 10 kilos, the survival rate was 43, but what we're seeing in this new  study published by Dr. Menon is that the survival is much higher. As a result, this is creating a new unique patient population that again may not fit  in the traditional intermittent, continuous, or peritoneal dialysis options. These patients that survive infancy are becoming more complex and they need something in between.  A lot of the literature is now starting to look at using PERT, which I like to refer to as the new SLED.  Traditionally PERT is a prolonged intermittent renal replacement therapy and that term is  reserved for when you're using an intermittent therapy on a CRRT-based machinery versus SLED,  which is the term that's used if you're using a prolonged intermittent therapy on a dialysis machine. I think this is why PERT is becoming much more prevalent in the literature.  You can see the differences here of how it's prescribed. It isn't continuous. It's an on and off therapy, but it really provides a therapy for a unique patient population  that doesn't fit in either category. Some of those would be the infants. Going from a 24-hour therapy to four hours on an adult HD machine may not be tolerated  initially by infants and so they get PERT on continuous when there may be something that's different.  Subject diseases, those who have structurally abnormal hearts that don't always tolerate complete fluid shifts may benefit from being on a PERT-type therapy.  It's a great translational therapy and that is really where it's being reported in the literature, minimal pediatric literature at this point, but it's being used in the adult  setting as a translational therapy. It's also being reported in the new mobility literature specifically to renal replacement therapies looking at improving rehab.  Getting patients up and about when they're ready to start rehab but still attached to a continuous therapy, PERT is becoming the option for these.  I think we will hear more and more about PERT. I think it is a unique patient population and a unique therapy that is going to be coming to the forefront.  As with most minimal literature in the pediatrics, I could only find one study. It was published in 2012 as well looking specifically at PERT versus continuous therapies and also  looking at survival. As you can see, there was very little differences between the patient populations, that continuous versus not continuous, as well as survival.  No different than your traditional literature, the survival was the same pretty much between the two. What was different is how sick the patient population is.  Those that were sicker didn't survive, which is very consistent in other therapies.  Overall, the 28-day mortality was 71.4%, which is very much in line with what we are seeing in the current literature with continuous renal replacement therapies.  Now we got to talk about the old that's become new again. In the early days, peritoneal dialysis was first line for critical care because it was really all we had.  But the advancements in other therapies such as continuous renal replacement therapies,  the advancement even in hemodialysis machineries and capabilities has sort of pushed peritoneal  dialysis down to a second tier and being reserved for a specific patient population, but maybe not being considered in patients that we had previously been considered.  Certainly, it still remains the first line of therapy for infants when it's appropriate. However, there are a large group of infants that do not qualify and have comorbidities  or contraindications for getting peritoneal dialysis.  But again, I think PD is going to play a bigger role in critical care, especially in pediatric critical care nephrology.  It may not be appropriate for everybody, but this is a study that was published by Dr. Kajkowski in 2015, looking again at a unique patient population, looking at the congenital  heart disease patient population, specifically those who require repair and cardiopulmonary bypass during repair. So this study was conducted at Cincinnati Children's.  It enrolled 84 infants with age-matched similar surgeries, and they were randomized into two different groups.  42 received peritoneal dialysis catheters and 42 received standard therapy, which included diuretics and any other therapies that they may have done.  And overall, in the published data, there were two significant data points that jumped out.  The time to negative fluid balance was significantly less in those patients who received peritoneal  dialysis, likely related to being able to remove fluid without having to use excessive diuretics.  And additionally, they were extubated sooner than the standard treatment, so getting them off the ventilator.  So this is a unique patient population that we may need to think about using an old therapy as a newer therapy more frequently. What's new in pediatrics?  And probably for me who have been in this field, for those of us who have been in this field a long time, the most exciting news in renal replacement therapies as it relates  to pediatrics is that we now have machinery that is dedicated to the patient populations that we are looking at.  So we have a neonatal specific CRT machines that specifically fit our smallest of small patients.  Additionally, we have pediatric software for the traditional machines that we have used. So we now have software that has safety features and prescriptive ranges that adapt to the  patient population that we're seeing, that 9 kilo, 10 kilo patient population. Along with that, we are starting to see pediatric specific CRT circuit sizes and filters, all  of which change how we can do renal replacement therapy, how we can select modalities. So now coming into the future, we will have machines that are dedicated to us, not an  adult machine that we are working at adapting. I think ultimately what we have realized over the last three decades is that one size does not fit all.  One modality may fit 85% of your patient population, but there may be a unique patient population that we need to pay attention to that we need to provide a different therapy for.  And that's why I'm excited to see these new, these old, but new therapies that are coming  back, peritoneal dialysis for a patient population using newer machineries for a patient population and PERT, which is now becoming a little bit more available.  So to wrap us up, renal replacement selection, especially modality, remains controversial. And while there is data to support one versus the other, it is still a very controversial  decision and ultimately will likely land on institutional and provider preferences, unless there is a unique indication that you're targeting.  These old modalities that served a unique patient population years ago are now going  to serve a different unique patient population, specifically PERT, specifically SLEDS, specifically peritoneal dialysis. And for us in pediatrics, the future is bright.  With the new rollout of neonatal and pediatric specifically designed technologies, we will  be able to provide therapies that have been dedicated and designed for the patient population that we are caring for.  And with that, I will end the session and then we will be having a question and answer session immediately after.

Video Summary

This session on pediatric critical care nephrology discusses the impact of fluid on patients in the ICU, both under and over fluid overload, as well as the appropriate treatment and timing for fluid administration. The session also explores AKI biomarkers and their use at the bedside, as well as the selection of renal replacement therapies for AKI. The speakers highlight the detrimental effects of excess fluid and the importance of balancing life-saving therapies with the risks of fluid overload. They discuss the current practices and guidelines for fluid management in the pediatric ICU, emphasizing the need for more conservative fluid management. The session also addresses the use of biomarkers to predict and diagnose AKI, and the role of biomarkers in guiding treatment decisions. The speakers advocate for a shift in culture and decision-making, where fluids are considered as medications and receive the same attention and consideration as other treatments. They conclude by emphasizing the need for reevaluating current practices and adopting a more patient-centered approach to fluid management and renal replacement therapy selection.

Asset Subtitle

Renal, Pharmacology, 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 basics and advances in the delivery of continuous renal replacement therapy
Review the current state of biomarkers to assess renal function in the pediatric ICU
Compare the different modes of renal replacement therapy available in the pediatric ICU

Impact on Over- and Underhydration on Outcomes in the Pediatric ICU
Matthew Barhight

Biomarkers in the Management of Acute Kidney Injury: Fact or Fiction
Rajit Basu

Modes of Renal Replacement Therapy: Old, New, and Everything in Between
Theresa Mottes

Meta Tag

Content Type Presentation

Knowledge Area Renal

Knowledge Area Pharmacology

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Kidney

Tag Renal Replacement Therapy

Tag Fluids Resuscitation Management

Year 2021

Keywords

pediatric critical care nephrology

fluid impact on patients

ICU fluid overload

fluid administration timing

AKI biomarkers

renal replacement therapies

conservative fluid management

biomarkers in AKI prediction

patient-centered fluid management

	Society of Critical Care Medicine 500 Midway Drive Mount Prospect, IL 60056 USA Phone: +1 847 827-6888 Fax: +1 847 439-7226 Email: support@sccm.org	Contact Us About SCCM Newsroom Advertising & Sponsorship DONATE	MySCCM LearnICU Patients & Families Surviving Sepsis Campaign Critical Care Societies Collaborative	GET OUR NEWSLETTER
© Society of Critical Care Medicine. All rights reserved. \| Privacy Statement \| Terms & Conditions The Society of Critical Care Medicine, SCCM, and Critical Care Congress are registered trademarks of the Society of Critical Care Medicine.