So I'm going to talk about nutritional therapy and pediatric critical illness. This is a topic that I have spent quite a long time working on from a research standpoint and clinically, both at my prior institution and then current institution. There we go. I have no disclosures other than some NIH funding, which I don't think counts here. And then learning objectives are really to go over the metabolic stress response, guideline recommendations for estimating energy expenditure in critical illness, going over protein balance, malnutrition, and then kind of a best practice guideline for bedside nutrient delivery. We'll start out with a metabolic stress response. And this is sort of the take home, really, in terms of what might be on the board exam in terms of starvation versus metabolic stress. So in starvation, energy expenditure is down, whereas in the stress response, it's variable. Hormone counter-regulatory capacity is preserved in starvation, but altered in stress. Primary fuels are fat in starvation, but in stress response are amino acids, glucose, and triglycerides. Ketone use is increased in starvation, but less so in the stress response. Protein breakdown is minimal in starvation, but accelerated in the stress response. And you have gradual loss of body stores in starvation, or rapid loss of body stores in the stress response. And then you can see the responses to gluconeogenesis, hepatic protein synthesis, and organ function. Importantly, provision of energy, so provision of nutrients, carbohydrates, lipids in starvation reverses the loss of body stores, but does not reverse the loss of body stores during the stress response. And that's an important distinction. So now we'll switch kind of to how do we estimate energy expenditure and what are the guidelines. So this is a guide, and again, guidelines are easily testable material because it's national norms printed, published. So these are from 2017, fair game for the board exams, long enough that the questions could have permeated into the board exam. So based on observational cohort study, the recommendation underlined in red is that we suggest that measured energy expenditure by indirect calorimetry be used to determine energy requirements and guide prescription of daily energy goal. Pragmatically, most units don't have access to indirect calorimetry for all of their patients. So then the subsequent recommendation that if you don't have IC measurement available, that you will use Schofield or WHO calculations or equations without the addition of stress factors. And that's probably the most important thing about the updated guideline is don't use stress factors. So the resting energy expenditure is what you should be providing. And then the target energy intake is at least 2 3rds of prescribed daily energy requirement by the end of the first week in the PICU. So, right, if you're not achieving that goal in the first couple of days, that's okay on the question, by the end of the first week in the PICU for the general critically ill patient. And these are all based on relatively poor quality data and weak recommendations, but this is what's in the guideline, so it's fair game for the test. So kind of wanted to review before I go into a little bit about indirect calorimetry, substrate oxidation, which is energy production in humans. So all of the carbon-based nutrients, carbohydrates, protein, and fat are oxidized to carbon dioxide, water, and heat. Direct calorimetry measures heat generation. Pragmatically, nobody does this in the ICU. And then indirect calorimetry, which is the recommended method to measure resting energy expenditure, is that you're measuring oxygen consumption and carbon dioxide production, which is then using the modified Greer equation, allows you to calculate resting energy expenditure and steady state, and that the respiratory quotient is another piece of the puzzle that might show up on the board exam, which is the ratio of carbon dioxide production over oxygen consumption. And this is kind of the table of what might show up, right? You might get a question asking you, giving you an RQ and asking you if this patient is underfed or overfed, for example. So carbohydrates result in a predominant as a predominant substrate result in an RQ of one, lipid 0.7, protein 0.8. And then if you're overfeeding your patient carbohydrates and causing lipogenesis, you'll have a RQ greater than a one. That's an easy test question. And then if your RQ is less than 0.7, it suggests the patient is underfed. And the clinical relevance in terms of lipogenesis and carbohydrate excess is that you have an increase in CO2 production, which may create difficulties liberating from mechanical ventilation. So REE prediction, the reason the guidelines say IC is the most accurate way is that equation estimated resting energy expenditure is woefully inaccurate. That's true in multiple studies. So you might maybe off by 10 to 20% or more if you're basing it on equation estimates. And then if you're adding stress factors, you're likely even more off in terms of comparison to measured resting energy expenditure. And so, and then in studies that have looked at indirect calorimetry compared to equation estimates, resting energy expenditure was in fact not influenced by severity of illness, diagnostic category, nutritional status or biochemical status. And importantly, this is energy, not protein requirement. So indirect calorimetry can be done on intubated and non-intubated patients. This is a picture of me in the PICU. Actually, it's my daughter under the bubble as my, I didn't have to get consent for taking a picture of a patient. So this is many years ago. She searches this picture out actually on the internet regularly to be like, look, mom, I'm famous. And so you're hooking up a sensor at the end of the, start at the endotracheal tube or at the expiratory, and at the expiratory loom of the ventilator to give oxygen consumption and CO2 production. And then using the modified Weir equation. And that actually gives you, the machine gives you the respiratory expiratory quotient, which at steady state is analogous to the respiratory quotient. And then you can do it in non-intubated patients as well in a bubble. But again, it's time consuming, technically challenging, difficult. So most places aren't doing it for all patients. So why does energy balance, overfeeding and underfeeding matter? So both over, it's the Goldilocks phenomenon, right? You gotta get it just right. Because overfeeding and underfeeding, both can cause delayed weaning from mechanical ventilation, right? Overfeeding, net lipogenesis, hepatic steatosis, increased CO2 production, ventilatory burden, hyperglycemia. Underfeeding, malnutrition, loss of lean body mass, and failure to meet protein and calorie requirements. All of which are associated variably with poor outcomes. So then protein balance, really the goal is about preservation of lean body mass. And again, back to the SCCM Aspen Nutrition Guidelines for the critically ill child. Minimum protein intake of 1.5 grams per kilo per day will be the answer on a board question asking you about what is the protein requirement or what are the recommended minimum protein requirements for critically ill children. That being said, this is different from, you know, healthy child out there RDA values. And there remain questions regarding should an enteral versus a parenteral recommendation be the same number that relates to bioavailability. And then the optimal protein dose associated with improved clinical outcomes is unknown. And specifically unknown for a whole variety of different conditions that we see in the Pediatric Intensive Care Unit. And overall, the quality of evidence is moderate. And so what's happening in terms of protein catabolism after major stress and surgery? You have protein breakdown. You have redirection of amino acids. So to create a free amino acid pool within the bloodstream for the production of acute phase proteins. And for the immune response. And so that's a short term adaptation to stress. But in the long term can be maladaptive in terms of loss of lean body mass, loss of respiratory muscle function, and even in extreme cases, loss of cardiac function. And so in this diagram, where you see a plus sign, it's an adaptation to short term stress. And then when you see the minus sign, that is the sort of long term negative consequence downstream of what may happen if you don't provide adequate protein and address protein turnover. So whole body protein turnover. You have in critical illness. You have both increased protein synthesis, but also increased protein breakdown. And the breakdown is typically more than the synthesis. And so that results in a negative protein balance. And then skeletal muscle protein breakdown and loss of lean body mass. The requirements to achieve a positive protein balance are a requisite protein intake, but also a minimum carbohydrate intake. And this is demonstrated in the literature. Somewhere around 50 to 60 kcal per kilo per day, which is why the Aspen recommendation is two thirds of energy goal by the first week of critical illness. So that that protein that you're delivering can actually do what you're expecting it to do. And then factors that predict optimal protein delivery in the PICU are time to initiating enteral nutrition after admission and days. The route of enteral nutrition delivery with post-pyloric feeds being associated with an improved delivery of overall goal calories and protein. Total duration of enteral nutrition interruption over the course of the first week, like for procedures, MRI, whatever reason, or for feeding intolerance. The presence of a dedicated PICU dietician is associated with improved nutritional outcomes. And moderate or larger size PICU is also associated with improved outcomes, but that's likely associated with the ability to provide a PICU dietician. And then malnutrition. So I'll go over some hospital-acquired macronutrient malnutrition and then micronutrient deficiencies. Actually, I'm gonna start with the micronutrient deficiencies. So low micronutrient concentrations. Again, this is low likelihood of being a question on the boards, but it could show up. So low micronutrient concentrations do not necessarily reflect deficiency states. It may be redistribution or adaptive response. It is unclear. What is clear is that multiple studies have been done to try to replace micronutrients with no effect or harm to the patient. And so replacing micronutrients is typically not going to be the appropriate answer on the question because we don't have data to support that practice. Dietary reference intakes are estimated from healthy children. We do not have data in what appropriate micronutrient needs are in critically ill children. There is some data in adults. And the current recommendation is to simply provide micronutrients at reference intake requirements for patient age and that more studies are needed. So this was published in 2013 by Nilesh Mehta's group and provides a conceptual framework to define pediatric malnutrition. A lot of this is not new in terms of, this is things we learned in pediatric residency, but could be given the association between malnutrition, both undernourished and overnourished, association with poor outcomes during critical illness could be an aspect of a board exam in terms of both etiology and chronicity and just the concept really that is both undernutrition and overnutrition or obesity are associated with worse outcomes of critical illness. And the outcomes include loss of lean body mass in terms of malnutrition that's preexisting or acquired during the hospital stay, muscle weakness, potentially development or intellectual delay, risk of infection for patients who have preexisting or acquired malnutrition during the ICU stay, immune dysfunction, delayed mood healing, and prolonged hospital stay. And then bedside nutrient delivery in terms of best practice and impact on clinical outcomes. And then I wanted to briefly go over because it can come up and it's often part of our practice in terms of what are routine fasting guidelines preoperatively for children. And so I think as a field we don't necessarily review the American Society of Anesthesiology guidelines, but they're very relevant to our practice. There are some differences between AAP and American Society of ASA guidelines and then European guidelines are again different, which begs the question of, well, who's really right? I can't answer that. And so the AAP recommends clear fluids up to two hours prior to anesthesia, milk or solids up to four hours and six hours. So it's the two, four, six rule. The American Society of Anesthesiologists say six hour fast from non-human milk or infant formula and then four hour fast from breast milk preoperatively. And so the goal is really to avoid prolonged fasting in pediatric patients. So the two, four, six rule, so fluids two to three hours prior to surgery. The data says that it does not influence gastric volume pH, emptying or risk of aspiration. Now, there are high risk children, right, so obese who have dysmotility. How many of these kids are in their ICUs, right? Ileus are on opioid infusions. And so there is no actual evidence to guide this strategy. So it really has to be a conversation with your anesthesiologist. So these two, four, six rules in the majority of patients in our PICU may not apply. And then there is interesting data in the form of carbohydrate loading preoperatively can shift patients from the fasted to fed state and result in decreased insulin resistance, modulate the postoperative stress response in a favorable fashion, decrease protein catabolism, muscle loss and preserve muscle function postoperatively and may be associated with reduced hospital length of stay postoperatively. One of the controversies ongoing, so to speak, in our field is gastric versus postpyloric. Some units are gastric feeders and some are postpyloric. And it's very strongly held opinions about what's right. The data are not so conclusive and actually relate largely to physician behavior. This is an old study from Kathy Miertz from Cheston, 2004. Small study looking at continuous feeds, gastric or small bowel. Really, the take home was that the daily calorie goal was more likely to be achieved in the postpyloric fed group rather than the gastric group. But my suspicion is this actually relates to physician behavior and what you do in response to feeding intolerance or emesis when someone's gastrically fed versus postpyloric feeding. There was no difference in microaspiration, tube displacement, enteral nutrition tolerance between the groups. And importantly, it wasn't detected to, it wasn't powered to detect mortality or other meaningful outcomes. And they used an inadequate tool to detect aspiration. So it doesn't say whether or not gastric versus postpyloric feeds were associated with aspiration or not. And then they had issues in terms of group allocation, whether or not patients actually got in the small bowel group because of difficulty placing tubes. We've all had that experience. And then the feed advancement was actually directed at the discretion of bedside nurses. So some problems with this trial, but it is kind of some of the data we have. A more recent study from Anne-Marie Brown from 2021 looked at continuous versus bolus feeds with a protocolized feed advancement guideline. They looked at gastric residual volumes as an independent variable or driver of enteral nutrition practice. There were fewer interrupt, the bolus fed group actually had greater percentage of goal calories and protein delivery. And the hypothesis really surrounding the advantages of gastric feeding was it's physiologic, it's bolus feeds. You allow for appropriate gastrointestinal function, which I'll talk about in my next talk. And then the majority of interruptions for the sites that were randomized to testing gastric residual volumes were due to gastric residual volumes. And then importantly, true feeding intolerance or emesis was never preceded by a larger gastric residual volume. And so it calls into a question a lot of our practices. And so some of this data and expert opinion are why the Aspen guidelines currently recommend gastric feeding over post-pyloric feeding and only post-pyloric feeding if patients fail to tolerate gastric feeds or have a pre-existing contraindication to gastric feeding. So how do we improve macronutrient delivery? Essentially, it's assessing the requirement. The guideline essentially goes through assess the requirements that the patient needs, provide a recommendation for energy and protein prescription, provide it in a systematic fashion through a feeding guideline so that you can deliver it. And so one of the factors that improve time-to-reach enteral nutrition goal are simply the presence of a nutritional guideline that you follow in your unit. The PAPANIC trial is fair game for the boards. Published in 2016, evaluated early versus late parenteral nutrition in critically ill children. Parenteral nutrition was started within 24 hours. If enteral nutrition did not reach 80% of goal calories. There are some questions about the study in terms of overfeeding IV nutrition. And then in the other group, parenteral nutrition was started on day eight. The take home from that study was that the late parenteral nutrition group had a lower rate of new infection, airway or bloodstream infections, and then a shorter PICU length of stay and a higher likelihood of discharge alive. This sort of closed the door on early parenteral nutrition for most critically ill patient populations. So on the exam, the early parenteral nutrition is not going to be the right answer for your patient. Pick something else. And they have long term follow up studies now demonstrating differences in neurologic outcome, multiple metrics. And then complications for parenteral nutrition include CLABSIs, PN-associated liver disease, phlebitis, and the overall strategy should be using the gut when it works in early enteral nutrition utilization. And then planning a PN prescription for patients who fail to initiate an advance on enteral nutrition is a balanced lipid, protein, and carbohydrate prescription. And then importantly, cardiovascular meds and enteral nutrition in the PICU, they're actually, this is from Panchal and Teresa McHale's group in 2016. On day one, looking at the vasoactive inotrope score for patients who were and were not fed just as a matter of routine physician practice. So a VIS score of 10 corresponds to like a norepi of 0.1, dopamine of 10, w-amino 10, epi of 0.1. There is no difference in VIS score for patients who were and were not fed. And importantly, no difference in adverse GI outcomes related to patients who were and weren't fed across VIS scores. So surviving sepsis guidelines based on some of this type of literature recommends enteral nutrition is the preferred method of feeding after initial resuscitation to achieve goal feeds within the first seven days of PICU admission. They suggest against supplementing lipids, against the routine measurement of gastric residual volumes, which I showed you some of that data, where that comes from, and that administering enteral feeds in septic patients through a gastric tube rather than a post-pyloric tube as the first line, and then against the routine use of prokinetic agents because they have no data for their efficacy in our patient population. And so the pragmatic approach is identifying vulnerable at-risk patients, creating an individualized energy and protein prescription, hopefully with the aid of a dietician, providing, initiating early enteral nutrition with a goal to get there at seven days for patients after initial hemodynamic stability is obtained, and then monitoring for intolerance if patients are intolerant, stop, and then restart. And then there is no role based on the literature for early parenteral nutrition within the first days of critical illness. And unfortunately, there's no magic fit all therapies for this heterogeneous population. That's the caveat. And I'm going to skip that because I'm out of time as a summary. And here's my email address if you guys have questions. Thank you.

pediatric critical illness

nutritional therapy

energy expenditure

enteral nutrition

protein balance

feeding intolerance