All right, good evening. We are now at our next session. We have an exciting session planned on nutrition therapy in the critically ill child. I would request all our attendees to take their seats as soon as possible and continue to carry conversations outside from the previous session, which I'm sure was very engrossing and exciting. And before we get started, I'd like to introduce myself. I'm Vijay Srinivasan, a pediatric intensivist from the Children's Hospital of Philadelphia. Yes, I know, right. And thank you all for being here this afternoon to listen to our exciting slate of speakers who are experts in the field of critical illness nutrition in the critically ill child. I have a few housekeeping remarks. Please move to the center in the front to fill in all the empty seats as much as you can. Please note the location of the exit doors in case we have a fire. Hopefully that won't happen. Please silence your cell phone and be respectful of keeping your voices low. And I would also like to remind you that we have to limit our times to the speaker allotted times. It's three speakers over the hour, 15 minutes per speaker, five minutes for questions, and I'm sure there will be lots of questions coming. Please ask these questions outside and continue these conversations because there's going to be more questions than answers. Information about the continuing education credit is also going to be available on the Congress app, and please take a moment to fill it out and get your credit for this. And I would request all speakers to disclose any conflicts, including any new ones that may have emerged since the time of declaration. And lastly, please be mindful that if you're tweeting this, be respectful and follow the guidelines of social media. So with that, I'd like to thank you and welcome all our speakers. We have Dr. Nilesh Mehta, who is a professor of anesthesia and critical care medicine at Boston Children's Hospital, who will be opening the slate of topics this afternoon. He will be talking on assessing nutrition in the critically ill child. Dr. Mehta. Thank you. Thanks, Vijay. I promise not to start any fires. But it might be close. Thank you all for coming. It's a pleasure. I'm charged to speak about the challenges with determining nutritional needs. It's a tall order, but let's give it a shot. I have nothing to disclose for the purpose of this talk. I will not be talking about any commercial products. In an attempt to speak about nutritional needs determination, I will focus on macronutrient needs, essentially energy and protein. And before we get to the energy and protein needs, some outcomes data, we need to focus on the basic cellular metabolism during the critical illness stress response. I think that guides us to get to the rationale for why we provide and what we provide and when. So we'll do a little bit of that, followed by some discussions about the energy and protein requirements, particularly focusing on what are the outcome relationships that suggest the doses that we might do. And then I'll end with a brief outline, a sketch, if you like, of the current concept of nutrient delivery strategy, a possible optimal strategy of our times, which will continue to evolve over time as new literature emerges. The metabolic response to stress forms the basic foundation for guiding nutrition therapy during critical illness. Metabolic stress response was described by Sir Cuthbertson, the figure on top. He was a biochemist in Dublin in the 1920s and 30s and 40s, and then by Dr. Francis Moore, a transplant surgeon with interest in science and particularly metabolic response after surgery. Together they provided some of the foundational stones of this pretty impressive response that has evolutionary origins. Whether it's trauma, sepsis, burn, other types of critical illness, this response is driven by a cascade of intense neuroendocrine pathways. The essential feature of this response is to provide substrate to the injured individual in order to allow the individual to utilize endogenous substrate before he or she can then proceed to get exogenous energy sources, either as a hunter or a gatherer. And hence it was very critical during human evolution to have this response. It affects almost every pathway in the body. There is intense lipolysis, which releases a lot of free fatty acids and ketones, which are used as fuel for essential organs like the brain. The fatty acid oxidation requires an energy-rich and oxygen-rich environment with a functioning mitochondrion, which is not often a luxury an acutely ill patient has, and therefore during critical illness lipids may not be adequately utilized until the patient is ready with the mitochondrial process. There is also intense glycolysis, which releases a ton of glucose in the circulation, and because of insulin resistance, which simultaneously is present, there is hyperglycemia, which we have well described, and people like Vijay and others have studied the use of insulin to address this. But this glucose is essential again as a substrate for so many important organs. Perhaps the most important part of this stress response is the muscle breakdown. Muscle is sacrificed in order to provide essential amino acids. These are released into the circulation and then get reprioritized in an effort to form essential proteins that fight inflammation, that repair the tissue, that heal the wounds, and all this persists until the individual is ready. So again, very useful during evolution, but in the current era of modern medicine, modern surgery, kinder, gentler ventilation, good sedation, temperature control, this stress response has outlived, if you like, to some extent, and therefore there are clinical consequences today of the stress response that we should be aware of. They are mainly of two types. One is the energy burden that this stress response places on the cells and the individual. It's almost like a car being revved at a high speed, consuming a lot of fuel. And the energy expenditure here, depicted not very accurately as a straight dashed line, is significant, and it's something that we should be aware of and attempt to measure or get a sense of. In addition to that, there is, as we saw in the previous cartoon, a lot of endogenous substrate being mobilized, lipids and glycogen, to try to provide some endogenous energy. This is unfortunately very difficult to measure, but it is transient, but it is present in the first few days. The true energy expenditure looks something like this. It is unpredictable, it is dynamic, it is variable. It may be variable depending on the type and severity of illness, but not necessarily. And this is a cartoon that depicts some of the data from 1970s, where different types of injury and burn had quite an alarmingly hyper-metabolic response. You see some of those, for example, major burns, has up to 180% increase in the resting energy expenditure or basal metabolic rate. Hence, when you think about providing exogenous energy to a critically ill patient, one needs to account for the energy expenditure and therefore try to avoid underfeeding and get to at least something near the energy expenditure goal, but also account for the endogenous energy production in the first couple of days, so as not to overshoot and overfeed. And this is not always easy. In addition, as we discussed in the previous slide, not all substrate is adequately utilized in an optimal fashion. So if you give nutrition in certain composition with proportions of carbohydrate fats and lipids, it's not necessary that the body can utilize them in that same proportion. And I'll show you a couple of concepts related to that. So if there was some way in which we could peek into the cells and figure the nature and the severity of this cellular metabolism, that would be great. Essentially, humans consume carbon-based nutrients. We consume carbohydrate protein fats. If you break them down biochemically, it's essentially carbon, hydrogen, and oxygen. And to utilize them at a cellular level, they need to undergo oxidation. So oxygen is consumed in that process with the resultant release of carbon dioxide and water as byproducts. Heat is generated that maintains body homeostasis. And energy is produced that allows the cells to function. And this is essentially happening at a cellular level on a daily basis, on every minute. Unfortunately, we can't peek into the cells, but we might be able to get some surrogates of this essential substrate oxidation. And one of the previous attempts to measure this was based on measuring the heat produced. So if you see on the lower left the cartoon of the individual exercising on a treadmill with heat generated during this exercise being measured as one way of peeking into the cellular metabolism, clearly none of our patients can do this, and therefore we needed an alternative. This was called direct calorimetry because it actually did measure heat. Another option is to measure the oxygen consumption and the carbon dioxide production. Again, cannot do that at the cellular level, but you can measure it at its bulk level at the respiratory exchange happening at the respiratory interface. So if I knew every minute how much oxygen I consume and CO2 I produce, it gives me a summative idea of what my cellular metabolism is. This is the concept of indirect calorimetry, a misnomer because there's no heat involved here. It's indirect. Now, indirect calorimetry has a technology that allows one to measure gas exchange, which is V.O2, oxygen consumption, V.CO2, carbon dioxide production, at the respiratory interface. The ratio of the CO2 produced to oxygen consumed is the respiratory exchange ratio, which all the calorimeters are able to measure. If the individual is in steady state, if you look at the figure on the right, it's an output of many indirect calorimeters where V.O2 over time remains stable, which means nothing extraneous or intrinsic is happening to cause transient fluctuations in these values. The human is in steady state. In such conditions, the respiratory exchange ratio measured by indirect calorimetry mimics the respiratory quotient at the cellular level, and that's the beauty of this device, and that's what allows you then, by using knowledge about what these V.O2s and VCO2s relate to in form of kilocalories, because these are experiments done in the early 20th century, we then derive resting energy expenditure and then create figures like the one on the right. Calvin Long and his experiments generated this figure in the 1970s. Here's the biochemistry, and I won't bore you, but if you just take the example of carbohydrate C6H12O6 plus 6O2 and the oxygenation results in combustion releasing 6CO2 and 6 water molecules, the math adds up, you will see. Now, in this case, the carbohydrate combustion resulted in equal number of O2 consumed and CO2 produced. Therefore, the respiratory quotient, the ratio of CO2 to O2 in this case is 1.0, and as you can see, lipid and protein have less CO2 produced for the amount of oxygen consumed and have a lower RQ. The reason I belabor this point is in addition to energy expenditure, indirect calorimetry allows you to get a sense in humans consuming a mixed fuel as to what is the predominant substrate being utilized. So, example, if in this case here at the bottom, there was excess of carbohydrate being given and then utilized, the respiratory quotient would be higher than 1 or closer to 1, and that would give you some idea of substrate utilization in an individual. So, fairly useful device. The other burden is that of protein, and we at our group has looked into mass isotopic, stable isotopic techniques using mass spectrometer to track protein turnover in individuals. In this particular experiment, we looked at 19 children who underwent thoracic surgery, and using stable isotopic techniques, we can measure, as shown in the red bars across for the 19 patients, protein breakdown, and then shown in the gray bars, the protein synthesis indicated in grams per kg per day. In this case, as you can clearly see, in all these patients, the protein breakdown is much higher than the protein synthesis, resulting in a net negative protein balance, and this has been shown by our group and many others in a variety of conditions, and many of them have alarming rates of negative protein balance. If this continues, it would be harmful in the form of loss of muscle, and nowhere is it seen as strikingly as it is seen in children with severe burns. So, on the left here is a depiction of another stable isotopic technique, this time using intravenous tracers, and in the black bars, you see the protein breakdown, the white bars, protein synthesis, and the shaded bars showing the net protein balance, which in children with burn injury along the x-axis, you see alarmingly, even up to nine months, it is still significantly negative protein balance. This is nine months after injury. So, imagine the chronic burden of slowly diminishing lean body mass, and this is just an example of an extreme protein catabolism after critical illness. This insight into metabolism gives us the goals, the rationale for nutrient delivery, and essentially three. We want to try and provide optimal energy and protein to offset the burden that we just described on energy and protein. We want to do this without getting any of the complications of the artificial or special nutritional strategies that we use, enteral and parenteral. And our primary goal, as we outlined earlier, is to prevent muscle mass loss, to preserve it as much as possible. We do that by choosing the optimal dose, easier said than done, delivering it by the safest route. You have three options, enteral, parenteral, or a combination, and then at the right time, and what is that? So, let's look into that. If you used past data to guide your dose, there is a significant problem, because in the past 10 to 15 years, several of us have a myriad of studies and a lot of variety of patients where we've shown the energy expenditure in critically ill patients in modern times is nothing like it was for Calvin Long in the 1970s. In these studies here, I've listed some of them. This includes studies from our group and Pittsburgh, where patients with bone marrow transplant, patients undergoing cardiac bypass for congenital heart disease surgeries, patients with head trauma, patients with significant heterogeneous critical illness, they all show a preponderance of hypometabolism, as depicted in the cartoon there, that was not expected before. So, if you are using these past estimates, if you don't have indirect calorimeter and you're using the inaccurate estimates from equations, and if you struggle with energy delivery like most of us do, you could be all over the place, and in a setting of hypometabolism, a good chunk of your patients may unintentionally be overfed, and that could be a problem. And then there's this Goldilocks dilemma, which we are well aware of, and unfortunately, indirect calorimetry is the only device available that currently opens a window into what really is going on. And as far as protein is concerned, the muscle-wasting scenario, which we are stuck with, there are several options. These three are predominantly what's being used. Physical therapy, we've heard a lot about the benefits of that, particularly in combination with nutrition, is something that we need to look at. Pharmaconutrients and drugs have been used in burn injury, but not a lot in general PICU, but we focus mainly on trying to provide enough or optimal protein to offset the losses. Here are a few studies that suggest energy delivery in relation to outcomes. In our first Pediatric International Study, we used 500 children in 31 pediatric ICUs, and on the left I show you the adjusted odds of dying, mortality within 60 days, in relationship to the adequacy of energy provision, a percentage of the goal. And what you'll find is not the EN plus PN, not enteral plus parenteral, but only enteral energy delivery is significantly associated with mortality, and patients who, instead of getting a third of what was prescribed, even went up to two-thirds of the goal prescribed within the first week of critical illness, dramatically dropped the odds of mortality. And in this case, this was pretty striking. As a result of many such studies, which I would urge you to look at in the most recent SECM and Aspen Combined Guidelines, we've recommended that endocrinometry should be used. Try to get hold of it. Try to play with it. If you don't have one, use these equations with caution. Don't add stress factors to avoid unintentional overfeeding. But most importantly, when the goal is determined, there is no rush to get to the goal or above the goal. What we've shown is in most patients, within that first week of illness, if you get to two-thirds of that goal, you are good. And it's the sweet spot where you will not be underfed, and you will not be overfed as you're trying to shoot for an optimal target. This allows a lot of leeway when you practically deliver nutrients. This slide shows on the x-axis lean mass in burn patients, as shown with the dark circles, and in healthy patients, children, matched, as shown in the open circles. And in both these, there is a direct correlation between lean mass and functional outcome. Here, it's a peak torque measured by isokinetic dynamometer on the left. And it's very clear that while the patient with burns have significantly lower performance, both groups have a direct correlation between lean mass and outcome, functional outcome. And therefore, it is essential that we try to provide what we know best, is some degree of optimal protein to offset the losses to prevent lean mass loss. So in our second international study, we looked at what's happening with protein delivery. And this time, we had 60, almost 60 PICUs with 1,245 mechanically ventilated children. Here on the left, you see days in PICU with protein delivery, and you'll see by day seven, only 50% at a median or mean, but variation, there's a big spread with some getting barely any protein in the first seven days. And this is important because it resulted in a huge deficit, as shown here, almost one gram per kg per day theoretical deficit of protein. And this, on the left, we show the correlation with mortality again. And if you see as you march from 0% adequacy of protein, even getting above 60, 66, up to 80%, you get significant drops in mortality. And these were after adjustment for severity of illness. So it appears that based on these studies, protein intake adequacy is important. And we are not talking about large numbers, but even up to 1.5 grams was significantly improved. Time to EN initiation, EN interruption decreasing, and a dedicated ICU dietician, many of you know this, were factors that made EN protein adequacy more relevant. We've never shown PN protein to be related to outcome. It's always been enteral protein, which is related to outcome. So the guidelines picked, based on a lot of nitrogen balance studies, isotope studies, the number 1.5 grams per kg per day as a ballpark to shoot for optimal protein delivery, knowing that you'll barely get to one gram per kg in most ICUs. The optimal dose in a randomized controlled trial has not been yet determined, and it remains a question. So I'll end this with a practical concept figure for you as to how does one put these concepts into actual delivery. And a lot has happened in critical care. Many of these new studies have guided us in developing this. So here's the first two days of critical illness. On the x-axis is days since admission, so it might as well be the time course of critical illness. On the y-axis is the energy delivery. And the first two days, there is hemodynamic instability, there is ongoing resuscitation. Also, there is some amount of endogenous energy production, so there's no rush to pump in energy in these patients in the first 24, 48 hours for sure. We don't know exactly how much is produced, how long, but it's transient. We know that for sure. As you come to this period, you want to try and define a goal, and we recommend indirect calorimetry, if you can, to measure and get to a resting energy expenditure measured, or use equations within reason, being guarded, to come up with your goal. And this goal is not something you would try to achieve in the first couple of days, but rather shoot for at least two-thirds of this goal in the first week. So you see, this is a much more pragmatic and a nuanced view of energy delivery. Now, what's important is not to overfeed, and that's the zone we need to be careful of. And remember, this is not a straight line, so unless we have indirect calorimetry available on a routine basis, we will presume that it's a straight line for practical purposes. As we proceed along, by day two, we recommend early enteral nutrition, as depicted here, and usually stepwise enteral nutrition advancement until you get to that two-thirds of the goal. And this is a perfect scenario. Everything's great. You guys live in a great nutritionally conscious ICU, and your patients tolerate feeds. It actually happens most of the time, but not always. And in patients where you can't provide any enteral nutrition, many of us deal with these, or you can go beyond trophics. And we are good with trophics right now, but if you can go. This is where now you need to measure the risk-benefit of sustaining or continuing with this deficit shown in the shaded graph between what you need to get to and what you're delivering, and how long are you going to wait. And this is the concept of when can we start supplemental PN. Not too early, not day one, day two, but how long will you wait. And the jury's out there, and it might be an individualized decision, but most people would suggest that by day three to four you must be beginning to think about how am I going to make up the energy and how long am I willing to wait. And this is the concept of PN start at a pragmatic time. And what's more important is as the EN begins to steadily go up, once it gets to 50% of the goal, stop the PN and allow the EN to get back to where you are. What you've done is you've done this total enteral plus parenteral nutrition-related energy delivery within a reasonable goal, not overfed by not feeding early here and shooting up by starting PN thoughtfully and then stopping as soon as you can. As a result, you've done this fine balance between the benefit and risk of PN therapy. And this, I believe, is what most of us espouse to, and currently it is a summary of everything that we've learned in the last 10 years. So here are my take-home points. The dynamic stress response is an interesting physiology construct that must guide nutrition delivery. One must try to open the window to look into the cellular metabolism. And until we come up with better ways to do this, indirect calorimetry is a handy tool and something to acquire if possible. Prudent delivery targets. Just because you measured X doesn't mean you get there in two days. At least two-thirds or 80% of protein is what we say within the first week. Early EN is still the way to go, and you'll hear more from Sharon after this in terms of how we are optimizing EN even in the sickest and the most previously vulnerable patients. Trophic followed by stepwise advancement, and then prudent PN supplement where necessary. Eventually, what each of you do is an individualized plan rather than coming up with a recipe that applies to all your patients. That's a fool's errand, and we shouldn't be trying to do that. And finally, whatever we do, we must firmly be engaged in trying to look at the correlation with outcomes, especially patient-related outcomes like muscle mass preservation, but more importantly, functional outcomes, quality of life. And in the next two, three years, there's a lot of studies that will help guide us along this path. I thank you for your attention. Thank you, Vijay. Thank you, Dr. Betta, for beautifully walking us through the challenges of determining nutritional needs. We're now open for questions. I think we're running a little short on time, so maybe one or two quick questions, and we'll move on to our next speaker. It was so clear, Vijay. I have a question. Do you think preexisting nutrition status might influence your recommendations? In other words, someone who's more malnourished, particularly because of preexisting starvation or a similar condition, might benefit from more aggressive nutrition? Is there enough evidence for that? That's a great question, Vijay, and you're spot on. When we think about individualized plans, what goes into this individualized plan? The preexisting morbidity and the accrued nutritional deficits because of that morbidity. Even vulnerability in the form of preterm newborns and newborns who I would not paint in the same brush as some of the randomized controlled trials. And then taking into consideration perhaps the burden of the illness. But the nutritional status is probably the first one. And you'll hear from our speakers subsequently how I think assessment of nutritional status on admission still remains our main focus. The PN start, which is what you're alluding to in terms of aggressiveness. As you know, the PAPANIC trial did the very early versus the very late, forgive me for using my own way of describing it, PN strategies. In that the newborns, there was significant severe hypoglycemia with the delayed strategy, and the aggressive strategy was still harmful. So somewhere in between titrated, individualized, based on nutritional status is the answer. Let's try to prove that in a trial. Thank you. Thank you so much, Dr. Martha. Thank you. Our next speaker is Dr. Sharon Irving. Dr. Irving is an assistant professor at the School of Nursing at the University of Pennsylvania and has focused her work in critical illness nutrition in children. And she will be talking to us about feeding on vasopressors. Welcome, Dr. Irving. Good afternoon, everybody. Thank you. Thank you, Nilesh, for setting the stage for me. So how many of you in your PICUs right now will feed a child who's on vasopressin or vasoactive medications? That's good to know. So how did you make that decision? How did you get the culture in your ICU to go along with that decision? Because five, ten years ago, there was nobody going to feed any child that was on anything that looked like a vasoactive med. So I'm going to try to walk you through kind of what's in the literature in this regard and give you some tools by which to begin to make some of those decisions. So I, too, sadly, have no disclosure or conflict of interest. But I bring you greetings from University of Pennsylvania School of Nursing and Children's Hospital of Philadelphia, which is where I do my work. So what I'm going to try to point out for you today and make a little bit clearer is to look at the physiology of GI perfusion. So we talk a lot about when to feed and how to feed, but we have to remember and think about what is the perfusion because that's the thing that scares everybody and that's the thing that makes people hold back. And unfortunately, there is no definitive marker for how to measure that on a day-to-day basis. And then we'll look at some of the current literature and the evidence around feeding on vasopressin. So you've seen this, right? And Nilesh did a wonderful job of really walking you through that, so I don't have to, okay? What I will say to you, however, is when critical illness occurs, be it trauma, be it sepsis, be it burns, be it surgery, whatever it is, what happens is there's a cessation of nutrient intake. So we are no longer giving them. And he described for you very nicely the fact that we don't have those stores, particularly protein stores. So after that day two or three, maybe four in some patients, you begin to get that breakdown, okay? And so now you are at risk of breaking down muscle mass. Now layer on top of that a critically ill child for whatever reasons that you're going to put on any kind of vasopressor or inotropic med, and most people will be like, No, they're too sick to feed. We can't feed their gut. And why is that? So let's talk just a second about that splant neck circulation. It has an impact on feeding. So think about what you do when you are resuscitating. We give a lot of crystalloid, right? And we go through this whole thing of 20, 30, 40, up to 60, up to 70, up to 80, and sometimes 100 mLs per kilo, right, to resuscitate them. So where is all that fluid going? It's not just staying in the preload. Some of it is going elsewhere, and it may be that that elsewhere is in the small bowel, okay? It's in the distal bowel. We may not see that in everyday measurement, okay? So we don't necessarily know. But the things to remember about that is that the blood flow to our GI system is heterogeneic. It's not the same because of various layers that we have in the GI system. So it's different in different parts of the GI system. It affects this splant neck blood flow, right, affects what the mucosal barrier does. The mucosal barrier in our GI tract is an important component to think about when we are talking about entrally feeding somebody because it's the one thing that if it is not adequate, this can set your patient up to be at risk to fail those entral feeds. And then lastly, because of the gut permeability and what's happening, it has an effect on that digestion and absorption and can make people quickly say they're not tolerating feeds, right, because maybe they have abdominal distension, maybe they have emesis, maybe they have diarrhea. We can't even completely define what feeding intolerance is consistently. So all of this plays together, and all of the things that Nilesh just pointed out to you, this is why this worked together so nicely because he set up for you that background, and hopefully I'll be able to tell you what we think is happening and what the literature shows us. So I'm not going to take you too far down the physiology trail, no worries, But let's just think about this for a second, right? When you talk about gut permeability, we have these transmembrane proteins, claudins, occludins, junctional adhesion molecules, and tricellin. And those things help to keep these junctions really tight in our GI tract, right? And so long as those junctions are tight, the lumen stays very healthy. And the bacteria that needs to be in the lumen stays in the lumen. It is when those junctions begin to open for various reasons, one of which can be that we're not feeding that lumen, OK? Because the blood flow that needs to go there is what helps maintain some of these junctions. When those junctions begin to open, as this cartoon here is trying to depict for you, that's when you get what everybody talks about is that translocation, right? And that's what can cause some of the illnesses that we see and can put your patient at higher risk for multi-organ system dysfunction. In critical illness, what happens is you lose some of that mucosal barrier function. You get impaired intestinal epithelial cell function. There's a breakdown of those transmembranes that I just talked about. They break down. They loosen those junctions. And then you get that breach. That's what's happening, OK? All of this comes back to the fact that this splantic circulation combined with gut permeability is essential for successful enteral nutrition. Because that therapy, if you don't have that adequate splantic circulation, and the status of your gut permeability is what puts our patients at risk. So with that background, what's the concern, right? We're concerned that we're going to feed into a bowel that is compromised. But we don't have a way to really measure the extent of that compromise, OK? There's no tool. There's no scoring system. There's no biomarker. There's nothing at this point in time. And then the concern is, do we have impaired gut mucosa, right? And how are we going to measure that? We don't have a way to really measure that. And then there's an increase in gut oxygen demand over delivery, right? Because the feeling is that if we start feeding them, we're making their gut work harder so the demand is higher. But we don't really know if that oxygen delivery is meeting that demand. Because again, we've resuscitated. There may be edema in that gut, OK? We don't really know how that gut is working. And how many days do we go without feeding, which causes that villi, if I go back here, which causes this villi to lay down. And all of that together is what causes us to put our patients at risk for feeding intolerance. So what's the evidence? So I'll start with a couple of adult studies. And then I'll go to the pediatric studies. So this is from the 2016 Enteral and Parental Nutrition for the Critically Ill Adult, and that group by expert consensus. So when you do the guidelines and you come to expert consensus, it's an indication that there's not enough solid evidence out there to give you the information that you need. So the expert consensus said, in a setting of hemodynamic compromise or instability, EN should be withheld until the patient is fully resuscitated. Not just withheld, but until they're fully resuscitated. That goes right back to what Nilesh was just saying in that first two, three, four days while we're still in the resuscitation phase, we made that may not be the exact time to feed them, OK? And then when they are stable, we can initiate and or resume that enteral nutrition with caution. So you have to continue to watch your patient and see what's going on to be able to determine, are they tolerating it? And that might be the time that we start those trophic feeds, but continually watching them to see, when can we move that forward? Or do we need to add PN to help them to attain even that 50% or 60% of total volume that we want them to have to support them? So even those patients on vasopressin support, there is evidence that says we can feed them with caution. So this is a study from 2013 by Mansell. They looked at enteral nutrition and IV vasopressin therapy. They had 259 that met criteria. They screened 384. And this is all adult ICU, right? They had enteral feeds plus IV vasopressors. The specific vasopressors that they use, I have listed there, dopamine, epinephrine, norepinephrine, phenylephrine, and or vasopressin were the meds that they used. Their outcome that they were looking at, their aim, was to look at EN intolerance. They defined intolerance by a gastric residual volume that was greater than 300 mLs, emesis, bowel perforation, and or ischemia. Now, I'm going to tell you from all of the studies that I will list here today that we talk about intolerance, that's a variable. It's variable. And everybody describes it a little bit differently. I like to say that particularly if you use emesis, and people will say, well, if they're having emesis, they're not tolerating their feeds. But how do you really define and quantify that emesis, particularly in children? Is it a baby spit and somebody is calling it emesis? Are they really having emesis? Are they having a projectile emesis? It's very variable. So I caution you to use that trepidatiously. So what they found, and on the side here, you can see these are the drugs that they used. The initial starting dose, their mean, and their maxes. And that's what's here. And then vasopressin is down here at the bottom. So what they found is in this column here is weight base. So they went by per kilo. And again, we're talking an adult study. They just went by mics per minute. So if you look here in the norepinephrine equivalents, when they had patients by weight who were on about 0.15, they did well with tolerating enteral nutrition. In the non-weight base, when they just looked at mics per minute overall, when they had patients that were here in the 12.5, those patients tolerated it well. And the seven, when they were at seven, they were just on that borderline of tolerating it. When you get down here to dopamine, higher doses of dopamine than what we would usually do. But if they were in the mics per minute total, if they were at 552 or the 789, they tolerated enteral nutrition. Now, I tried to do the math. I'm a pediatric person. So I tried to look at this in the adult world and just kind of said, if you have a 75 kilo adult and looking at these numbers, these are numbers close to what we use in the pediatric world when we talk about per kilo. So basically, what they came out to say is that using norepinephrine, you can do pretty well. As you go up in some of these meds and dosing wise, whether it's per kilo or if it's per minute, as you can see, they didn't do so well tolerating enteral nutrition. Essentially, the increased EN tolerability with decreased maximum norepinephrine or norepinephrine equivalent in the other meds, they tolerated enteral nutrition. And that's what this is showing you here. If you look on this axis here, when they were at less than 2.5, and this is mics per minute, this is not weight based, they had up to 85% and better of tolerating enteral nutrition. So what does that tell you? That some of those patients who are not escalating and who are not on high doses can do well with enteral nutrition. So they concluded they had about a 65% survival to discharge out of their study. 75% of those participants tolerated EN well on the lower doses, as I just described. Norepinephrine, those doses were somewhere in, if you look at what most of us are used to looking at, is in this 0.16 mics per kilo per minute. Now, that's a high dose for us. But what I want to point out here is that if you can manage a patient on this amount or less, you can probably feed their gut. Phenylephrine, again, higher doses. But again, these patients tolerated it. Now, I don't want you to walk out of here and say, she said. Because we cannot extrapolate everything from the adult population into pediatrics. But it gives you food for thought. It gives you something to think about to say, I don't have to just wait the five, seven days or whatever that that patient is on those vasoactive medications to begin to feed. So in another study by Patel that was done in 2016, looking at early trophic feeds in mechanically ventilated patients, they had 66 adults. They screened about 490. And only 66 met their criteria. All of these patients were mechanically ventilated. They separated them into three groups. Those that had no feeds, those that had trophic feeds, which are described here, less than 600 kilocals per day, and then those that had greater than what the trophic feeds are. So greater than that 600 kilocals per day. And again, we're talking adults. And so what they found, and I gave you the chart here, but they really had very little that was significant in what they found. So there was no difference in mortality across their groups. The length of stay was lower in the patients that had the trophic feeds versus those with no enteral nutrition. And it was statistically significant. And these patients that got the trophic feeds also had better outcomes than the patients that were pushing towards full feeds. And again, with statistical significance. Telling us that maybe you can't get them to full feeds, but you can certainly put a little something in their gut to maintain gut health. Maintain the villi standing upward. Try to maintain those tight junctions. So feed tolerance was 87%, 97%, and 86% respectively across the group. So again, we see that that group that's sitting there right in the middle that was receiving trophic feeds, they did fairly well with getting some nutrition. No aspiration pneumonia. I'm sorry. Aspiration pneumonia in the no EN group was 6.7%. 0% of aspiration pneumonia in that group that was on trophic feeds. And then 7.2% in the higher group. So again, giving you some food for thought and a little bit of evidence to say, we can do this. We need to monitor our patients. We need to watch and see what's going on. There was no mesenteric ischemia. And I thought that was a really important point in this study, that they had no mesenteric ischemia in any of the groups that they were feeding. So what did they conclude? Early trophic feeds in mechanically ventilated patients. They had decreased days of mechanical ventilation. They had decreased length of stay. There was no aspiration pneumonia in the trophic fed group. And no mesenteric ischemia in any of the groups. So again, food for thought. So that's the adults. So what about the children? So Nilesh again alluded to and spoke about the guidelines that we did back in 2017. And these were mostly observational studies because in pediatrics, we don't have the luxury to have as many RCTs as our adult colleagues have. But they're very informative. They're very informative. And they give us the basis by which we can begin to develop some of those RCTs. So out of these studies, it suggests that EN within 24 or 48 hours in all critically ill children, Nilesh contraindicated. But we know now that was 2017. We know now that that first 24 to 48 hours may not be as essential as we thought it was. There is a risk of aspiration, but it's pretty low. There's always that risk of aspiration. Think about how we position our patients. If nothing else, to my nursing colleagues out here, we feed them. You can't just lay them flat all the time. Because if you fed me, if you fed most of us and just laid flat, you would have some aspiration. So we just have to think about some of those things as we go along. Gastric route is preferred. And why is that? Remember I said earlier, when we talk about splanctic circulation, you can have edema in that lower bowel, in the post-pyloric bowel. So gastric is preferred in critically ill children. And then the post-pyloric, although it's doable, it has been associated with an increase to attain goal. However, there's a prolonged time to initiate it, because you've got to get those tubes in, by whatever mechanism you're using to get them in. So there's that plus and minus. And now we know that with gastric feeds, most of these children can do well. So this is a study that was done in 2004 by King and colleagues. It was a retrospective study looking at 733 admissions. And they came down to 52 that met their criteria. And I looked at studies that were specific to vasoactive medications. Their criteria was they had to be on enteral feeds and cardiovascular medications in the same 24-hour period. And then the medications they looked at were similar. They used dopamine, dibutamine, epinephrine, norepinephrine, and phenylephrine. So what in this table right here was, I thought, interesting in that the most common combination that they used was dopamine and norepinephrine. Now, we don't use as much dopamine now as we did. But this was a study done in 2004 where dopamine was like the candy store. Everybody was using dopamine. And so that was the most frequent combination that they used. They found more issues with feeding interruptions than with intolerance. And so as you can see from this chart here, airway management was the reason that they had more feeding interruptions than anything else. They did not have as many GI feeding interruptions as they anticipated. It had to do with airway management. It had to do with procedures. And it had to do some with clinical changes. But as you can see, it goes down from here. 35 of their patients were all for airway management. And that's the bulk of what we see in our ICUs. They concluded the overall participants tolerated the feeds well. And they had no significant complications. They did have three patients that had some degree of GI bleeding. But they termed it not clinically relevant. So they didn't give any more descriptor of that. But they said it was not clinically relevant. And in fact, they only stopped feeds for a short period of time in those three patients. They had 29% of feeding interruptions were secondary to feeding intolerance. And they defined intolerance as abdominal distention, gastric residuals, and constipation. 70% were non-GI related. So again, think about why are we stopping feeds and when do we need to restart them? The study that most people are familiar with in pediatric patients in terms of vasoactive medications is by Panchal and Mikulov up in Wisconsin. They did a retrospective study. They actually looked at over, and it was multicenter, they did over 5,000 children. For this particular study in terms of vasoactive medications, 339 were cited in the study. They initiated EN within 48 hours of PICU admission. And they had to be in the PICU for at least four days. The medications are listed here, epinephrine, norepinephrine, vasopressin, milrinone, dopamine, and dibutamine. This chart here just gives you an idea. The dark faded are the kids that were not fed. And as you can see by the diagnosis distribution, this is pretty common in many of our PICUs. These are the patients that we see. And look at how many were not fed. Only the neurology patients had a higher percentage of being fed early. So what did they find? Age and weight were significant, but that makes sense, right? The younger children were fed earlier and they were smaller. And that was statistically significant for this group. Mortality in the fed group was better, almost half of what it was in the non-fed group. And PRISM-3 and predictors of death was lower in the fed group than in the non-fed group as well. All four days, these patients were getting vasoactive medications. But the amount and the fed group was the only time, only on day one was it significant that they had issues, if there were issues. But all four days, both groups were being fed and were receiving vasoactive medications and did well. So they concluded entral feeding is safe in children on vasoactive medications. There's no difference in mortality in their sample between the fed and the non-fed groups. Entral feeding was achieved in more than 50% of their participants. And 78% of them tolerated it and tolerated it well. And so how many of you were at the sepsis guidelines this morning? So hot off the presses, right? The new pediatric septic guidelines that just came out this month say, feed on vasoactive medications. Entral nutrition is preferred. Gastric versus post-pyloric, for the reasons that I pointed out to you. Don't take the time to measure gastric residual volume. Do not routinely use pro-kinetic agents. Now, that's going to be a culture change. So in conclusion, the evidence that we have to date suggests, and the pediatric sepsis guidelines that just came out all suggest, patients on vasoactive medications, both adult and pediatrics, they can be fed safely. Consideration of what we know about splantic circulation that I pointed out to you. What is the stage of your resuscitation? What vasoactive medication and at what dose? Is there hemodynamic stability that you're dealing with? And where are you planning to feed that patient, gastric or post-pyloric? And with that, I thank you very much for your time. Thank you, Dr. Irving, for a wonderful talk. In the interests of time, I'm going to request that the audience direct questions to Dr. Irving at the end of the session. I'm now going to invite Dr. Ben Albert to talk about nutrition in the surgically ill, critically ill child. Dr. Albert is an instructor at Boston Children's Hospital and at Harvard Medical School, and I'd like to welcome Dr. Albert. Thank you, Vijay. I realize that I'm the only thing between your current NPO status and some enteral nutrition with dinner. So for the interest of time, I will likely skip a couple of slides as we go through so that we don't run too much over. We're going to hone in a little bit on the surgical population of the patients that we take care of in the PICU, and I'll be giving you a brief overview of some of the things that are really important in that population. I have no financial disclosures or conflicts of interest. And we're going to talk briefly about preoperative, operative, and post-operative considerations in these patients. We'll talk about the nutritional risk factors and the current preoperative fasting guidelines, which have been evolving and changing. We're going to talk about operative considerations, specifically the ERAS, or the Enhanced Recovery After Surgery Protocols, that are now becoming more common in the pediatric population, and the post-operative considerations. And specifically, I'll take just a brief deep dive into a couple of different specific populations, ECMO, CDH, and intestinal failure, if we have a little bit. Well, we may have time. So malnutrition prior to surgery is something that's extremely prevalent. Specifically, the patients that we take care of in the PICU, they have longstanding comorbidities, either cardiovascular, musculoskeletal, or gastrointestinal comorbidities. And because of that, the malnutrition can be chronic, or they can have an acute exacerbation leading to an acute weight loss prior to surgery, which is important to think about before they go into the operating room. And malnutrition, including obesity, can affect surgical outcomes and complications. As an example of this, this is a recent study just published in 2018 that looked at 500 patients undergoing major bowel surgery. They had Crohn's disease, so a chronic comorbid condition. And as you can see by the data that's highlighted in red, the rate of surgical complication increased with the degree of malnutrition that the patients had. So before patients go in for surgery, in healthy children at least, the current American Society of Anesthesiology guidelines recommend six hours of fasting for solids, four hours for breast milk, and two hours for clear fluids. And we always need to remember that in the critically ill population, the things that we do, inflammation, all of our sedative drugs, mechanical ventilation, can impact gastric emptying. And so these might not apply to our critically ill children, but the healthy kids coming into the operating room that we're going to take care of post-operatively, these are the guidelines that they should be following. Now, although they're supposed to be, we haven't completely gotten rid of the dogma of NPO after midnight. We say that on our night rounds still. I still hear it being said. And the patients, obviously, if they're coming in for a 7 AM surgery, they're likely going to bed and then sleeping the entire night and coming in not having eaten or drinking anything before their surgery. This review that was published in 2018 took a summary of all the studies that have looked at fasting times. And just the clear fluids, which is recommended two hours, there are still some prolonged fasting times with averages of eight with ranges up to 21 to 24 hours, almost two days of fasting, even for clears. And so we still have a lot of work to do in this area. Now, gastric emptying, these guidelines come by the kinetics of how liquids and solids are emptied. Solids have a lag phase of up to about an hour and then have a linear degree of emptying, whereas liquids, especially clears, have a first order kinetic and rapidly clear, which is why they are now recommending that you can even drink clears or water up to two hours before surgery. The point of it is to have the stomach empty to reduce the complications after the induction of surgery and to reduce vomiting and pulmonary complications. But it's not necessary for them to be fasting for 8 to 12 hours as some of these patients are. And as I mentioned, in the ICU, there's a lot of things that affect this gastric emptying, so the current guidelines in our ICU patients might not apply. Now, one of the units that I work in in Boston is in the cardiac ICU. And ERAS has become a big component of some of the more common congenital heart lesions in the unit there. And a lot of the things that we're doing are to try to move the patients out of the unit and reduce a lot of the complications that they get when they stay in our unit longer. This was widespread in adult literature now, and it's just starting to pick up some steam in the pediatric literature. And there's a lot of data now, or emerging data, looking at appendectomies, bowel surgeries, urologic surgeries, and cardiac surgeries that are using this ERAS protocol to try to reduce complications, such as postoperative ileus because of all the pain medications that we give and not mobilizing patients early and they lie in the ICU beds with NG tubes not being able to take enteral nutrition. So some of the preoperative principles that have been developed into ERAS is to minimize the preoperative fasting period, as I had mentioned. And some units use Gatorade, and some institutions actually have a predefined solution that they drink to give them an oral carbohydrate load. It maintains glycogen stores and prevents catabolism postoperatively after their surgery, and also to avoid hyperosmotic bowel preps to reduce the incidence of bowel wall edema and hypovolemia that can result from these hyperosmotic bowel preps. Operative principles, the increasing use of regional pain services and pain catheters has really reduced the use of opioids. And the reduction of opioids have allowed for less postoperative ileus and improved gastric emptying to, again, start feeding patients earlier and to get them out of bed and to get them out of the unit. It was extremely common when patients had GI surgeries to come out of the operating room with an NG tube. And in the adult population, they're trying to no longer do that. And it really has been shown that nasogastric tubes delay the use of eating by mouth and have also increased the risk of pulmonary complications. And so the avoidance of that to hopefully feed kids earlier is part of the operative principles of ERAS. And then maintenance of uvolemic state. If they're drinking up to the time of surgery, they're not as hypovolemic. And there's not as much need to give a ton of fluid in the OR if they're hemodynamically stable. And that, again, reduces GI and bowel wall edema and allows them to take enteral nutrition earlier. Postoperatively, we try to do the things that reduce metabolic stress, such as aggressive nausea and vomiting control and fever control. We try to get them to take stuff by mouth as early as possible. We try to get them up and moving. There's not a lot of data in the pediatric population with regards to ERAS yet. But one study that was recently just published in 2020, this year, a couple of months ago, showed this ERAS protocol for surgical patients at an institution. And they looked at a pre-intervention cohort, which had the same characteristics of the ERAS protocol. And they showed, although not statistically significant, a reduction from about 235 hours in the unit down to about 155. And they showed the time to PO intake, which they labeled taking 120 mLs of PO intake, down from 65 hours down to 39 hours. And you can see across the board, there was less opiates used in the ERAS group. Just to flip into a few special populations, the ECMO population is one in which we struggle with. We don't have an ability to do indirect calorimetry yet, because it's not a closed circuit. Although there are some people that are starting to do this and investigate how to measure or accurately measure resting energy expenditure. But we're concerned about hemorrhage. We're concerned about neck. And we're concerned about perfusion to the gut. And so the enteral nutrition is almost always delayed in this population. And it's true that ECMO doesn't necessarily equal metabolic rest. There are patients who are on ECMO that are definitely hypermetabolic and have a higher resting energy expenditure need. Almost a decade ago now, Dr. Jaksic, and through the Aspen guidelines, came up with neonatal guidelines for ECMO. And they knew that already these patients are going to have a protracted catabolic stress period that's going to result in lean body mass loss. And they're going to have whole body protein degradation. So part of their recommendations, although not a lot of evidence, so a low grade of evidence, or they recommend higher than normal protein requirements and starting enteral feedings as soon as the patient is hemodynamically stable. A study that was done in 2018 by Armstrong and et al. at Boston Children's Hospital looked at 54 patients that were on ECMO. And as you can see here by the blue line, we don't do a lot of enteral nutrition in these patients quite yet. But almost less than 15% enteral nutrition in this population in the first seven days of ECMO. And 10% of the energy was delivered enterally in these patients. So still some work to do. Congenital diaphragmatic hernia is another population that we struggle to get enteral nutrition in. They have a lot of comorbidities, as you can imagine, like reflux, post-repair, and chronic lung disease, which increases their metabolic demand. And so it's very common for them to have a reduction in weight for a disease score, although it does appear to recover over time. In this study that looked at 200 babies with congenital diaphragmatic hernia, they followed them up 12 months after discharge from the PICU. And it was shown that if you had a patch repair, a lower birth weight, less than 2.3, sorry, less than 2.5 kilos, or inadequate protein intake, those were predictors of lower weight for age Z scores at one year after PICU discharge. This was a neat study that followed up patients up to 12 years old. It was published in Pediatrics in 2017. And you could see there was actually a dip up to about five years of height for age Z score, but then also recovered up until about at around 12 years of age. So a really interesting long-term study. And obviously, if they were congenital diaphragmatic hernia cannulated to ECMO, it was lower in that population than if they were non-ECMO congenital diaphragmatic hernia repair. I'm going to just pass by intestinal failure really quickly just for time, but just to show that if you have a diagnosis of NEC, you were seen at an intestinal care failure site or you had an intact ileocecal valve, those were associated with being able to achieve enteral autonomy, meaning your non-dependence of parental nutrition. And a length of about 41 centimeters of remaining bowel that was not resected also had the highest incidence of achieving enteral autonomy. So lastly, in part of Dr. Mehta's nutrition pin study, they published a sub-cohort of that international cohort looking at surgical patients in and of itself, which was about 40% of the entire data set. And just to highlight that, the protein that's being delivered into these surgical patients is very low, up to 0.2 compared to 2 grams of what was prescribed. So just in brief, I think the things that we still have left to do in this population is a lot. But I think that screening these patients and figuring out who is at risk of malnutrition is extremely important. I think that we need to continue to adapt and be conscious of the preoperative fasting guidelines for these patients. I think we need to be, as we heard from Nilesh, being really thoughtful about entering enteral nutrition very early and thinking, being thoughtful about parental nutrition and whether or not we need it and when we can actually take it off. And then new technology for measuring resting energy expenditure, especially in patients like the congenital diaphragmatic hernia populations, I think is going to be important in the years to come. Thank you very much. Thank you, Dr. Albert, for a very nice walk through the issues pertinent to the care of the surgical critically ill child. We're now open for questions for Dr. Albert as well as for Dr. Irving and also for Dr. Mehta. If anyone has any questions. Looks like we're all ready for our dinner, so enjoy. Thank you, everybody. Thank you to our speakers. Again, a big hand to Dr. Mehta, Dr. Irving, and Dr. Albert. Thank you.

nutrition therapy

critically ill children

energy requirements

protein requirements

metabolic stress response

carbohydrates

lipids

amino acids

feeding children

preoperative fasting