Hi there. Welcome everybody. This is Nutrition Support in the ICU. My name is Michelle Kozinecki. I'm a Certified Nutrition Support Clinician, a Certified Clinical Transplant Dietitian, and the Lead Clinical Dietitian at Fraynert Hospital in Milwaukee, Wisconsin. These are my disclosures. So my objectives today are to describe the role of the gut throughout the phases of critical care illness and recovery, review basic recommendations for the timing, route, and type of nutrition therapy for ICU patients, and identify potential impact of the amount and type of macronutrients provided to ICU patients. So before we get into the details, let's first consider this case. We have a 55-year-old African-American male with a new diagnosis of colon cancer and a past medical history of severe asthma. He's admitted to the hospital with flu and shortness of breath. By hospital day three, he develops pneumonia, an acute hypoxemic respiratory failure, and septic shock. This requires intubation and transfer to the ICU. From a nutrition standpoint, he's had poor oral intake with 13 pounds of weight loss over the past month, so this is 9% of his weight, bringing his BMI down to 22. Now this is where I start thinking about what's going to happen to this patient medically and nutritionally, and what can nutrition therapy prevent or possibly attenuate. When we're thinking about what's going on nutritionally with our patient, really we're thinking about metabolism, and the metabolic transitions during the phases of critical care are outlined here. These were from the ESPEN guideline about two years ago. The acute phase is divided into an early and late period. The more obvious consequences of the early acute phase are comprised of metabolic instabilities, and that includes hypercatabolism and a caloric debt. What's also going on, though, is proteolysis, which might lead our patients to become more sarcopenic, and in some cases, extremely sarcopenic. What's less obvious might be the component, though, of gut dysfunction. Okay, so I'm not going to spend too much time on this slide, but just to kick off the subject of gut dysfunction and how it relates to multiple organ dysfunction, just take five seconds to look these over, and I'll cover some of these topics in the next couple slides. Your intestinal barrier is made up of the epithelial cells, immune cells, and commensal bacteria. These work together through crosstalk signaling to maintain tight junctions and keep harmful substances out of your bloodstream. Unfortunately, in the ICU setting, there's a lot of things that can negatively impact gut health. The first thing that comes to mind, especially for me, is medications, particularly acid-reducing agents and antibiotics. 70% of hospitalized ICU patients receive antibiotics, and 35% of those antibiotic regimens might be unnecessary, and this can potentially increase the number of multidrug-resistant bacterial infections that we see. And then with patients who develop sepsis, shock, ischemia, and low-flow states who require resuscitation, this means that the microbiota that are there are competing for limited resources and have to survive under harsh and hostile conditions. Oftentimes, this is not possible. The result is extreme dysbiosis of the microbiome, as was seen in this study here. If you look at the bottom image, this is the spread of the gut microbiome or gut bacteria of healthy individuals enrolled in the American Gut Project. Right above that, you can see that on admission to the ICU, patients have already a dysbiotic microbiome, and upon discharge, it actually gets even more pronounced. Well, why does this matter, and what happens when things start to go wrong? Well, when there's a breach in the intestinal barrier and there's altered microflora, you start to see mucosal thinning, impaired tight junctions between the epithelial cells, and enterocyte apoptosis, or gut cell death. So this leads to gut-derived inflammation, emergence of a pathobiome, and that can happen within 48 hours and ultimately lead to multiple organ failure. So that brings us to the value of early enteral nutrition on gut dysfunction. Enteral nutrition, or EN, maintains epithelial barrier function, and deprivation leads to the loss of intestinal epithelial barrier function. So proliferation of enterocytes is preserved with EN because epithelial cells absorb nutrients directly from the GI tract to meet their nutritional requirements. In other words, it's essential that GI epithelial cells receive their nutrients intraluminally to guarantee cell division and differentiation. In one study, they found dysbiosis with parenteral nutrition as compared to enteral nutrition and impaired barrier and immune functions related to that. Supplementing only 20% of calories with enteral nutrition was able to reverse those dysbiotic changes that were seen. Because of these reasons, all guidelines recommend early EN over PN. This includes the 2015 Canadian Clinical Practice Guidelines, the 2016 Society of Critical Care Medicine and American Society of Parenteral and Enteral Nutrition Guidelines, and the European Society of Enteral and Parenteral Nutrition Guidelines from 2019. This means starting enteral nutrition within 48 hours of ICU admission. Coming back to our case patient who's in the ICU with respiratory failure and septic shock, he has now received four liters of IV fluids. Norepinephrine is running at 0.2 microns per kilogram per minute, and he has an acute kidney injury and is starting continuous renal replacement therapy. To me, I would think, well, because the benefits to the gut for enteral nutrition, that would be my first choice for providing nutrition therapy over parenteral nutrition, but there are some other things that should be considered. Some of the questions that need to be asked in terms of starting nutrition support therapy, whether it's enteral or parenteral, and how much to provide, how fast, is, is this patient currently malnourished? Are they at nutrition risk? Are they at risk for refeeding syndrome? And are they hemodynamically stable? First, is this patient malnourished? Well, let's look at the definitions of protein calorie malnutrition, which is a nutrition diagnosis that's made by the registered dietitian, and it's also a medical diagnosis once it's documented by the provider. So there's not one definition necessarily of malnutrition, but here are three that are commonly used and well known and accepted. So the first is the Aspen and Academy of Nutrition and Dietetics consensus characteristics from 2012. The second is the Global Leadership Initiative on Malnutrition or GLIMM. And then the third is Subjective Global Assessment, which has been around since 1987. So all of these definitions have very similar characteristics. All of them include a component of inflammation to recognize the role that inflammation plays in metabolism and body composition. All of them include reduced intake, weight loss, and muscle loss. And then the Global Leadership Initiative on Malnutrition and SGA also include impaired absorption and GI symptoms, whereas only the Global Leadership Initiative on Malnutrition looks at low BMI as a criteria. And then the Aspen and Consensus characteristics and SGA further look at nutrition-focused physical exam findings in terms of fat loss, edema, and then reduced grip strength by hand grip dynamometry. So for our patient who's had poor PO intake and 9% weight loss in the last one month, and with this nutrition-focused physical exam findings are likely to reveal muscle and fat loss, let's look at what that means. So regardless of the criteria that you use, yeah, this patient is likely going to be diagnosed with severe malnutrition. This is definitely something to be aware of because malnutrition is present in 20 to 50% of ICU patients, sometimes on hospital admission, and then up to almost 70% of patients experience a decline in their nutrition status during their hospitalization. Malnutrition is a huge problem when it comes to patient outcomes as well. So patients who are malnourished have four times the risk of developing a hospital-acquired pressure injury compared to those who are not malnourished, and they have poor wound healing on top of that. Patients who are malnourished are at two to five times the risk of surgical site infection and other nosocomial infections. Patients who are malnourished have longer hospital stays, more readmissions, and higher medical costs. And 45% of the patients who fall in the hospital are malnourished. In terms of mortality, you can see on the graph here, patients who are severely malnourished are at 47% probability of mortality after one year compared to patients who are well-nourished at only 10%. So our patient, our case patient, definitely meets the criteria for severe malnutrition, is at risk for all of those worse outcomes. But that's not the only question that you have to ask when you're trying to think, should I do or should I start nutrition support early and how aggressive should I be? The other question you have to ask is, are they at nutrition risk? And those are different things. So regardless of nutrition status, you're always going to want to think about this as well. So the purpose of a nutrition risk scoring system is to predict the probability of a better or worse outcome due to nutritional factors, and also to predict whether nutritional treatment or intervention is likely to influence that outcome. So on this page is one of those tools. It is the Nutrix scoring system that the variables include age, Apache 2, SOFA, number of comorbidities, days from hospital to ICU admission, and if it's available, IL-6. And if IL-6 is not available, this tool has been validated as a modified Nutrix score without that variable. So let's take a look at our case patient. With age 55 and Apache 2 score of 22, a SOFA score of 7, two comorbidities, having been admitted to the ICU two days after hospital admission, even without an IL-6 available, his score is 6, and anything above a score of 5 is considered nutritionally at risk. So looking at the interventions then, for anyone with a high nutrition risk score, now remember these are the patients who are associated with worse clinical outcomes like mortality and duration of ventilation. These are the patients who will likely benefit from early aggressive calorie and protein provision. Compared with patients who have a lower score and are at lower malnutrition risk, maybe you don't need to be as aggressive in terms of reaching calorie and protein goals as early. So the other factor when considering how aggressive and how fast you should ramp up nutrition support, be it enteral or parenteral nutrition, is, is this patient at risk for refeeding syndrome? Now remember refeeding syndrome is when a patient is in a starvation state and then you reintroduce a carbohydrate source, causing insulin to drag the carbohydrate into the cell and with it electrolytes follow, resulting in a decrease in serum potassium, phosphorus, and or magnesium levels. The risk factors for refeeding syndrome are poor PO intake, which our patient did have, weight loss, which our patient did have, muscle and fat loss, which they likely did have, higher risk comorbidities, and already low to normal or low electrolytes. So our patient is at risk for refeeding syndrome. In terms of how to treat that or how to prevent refeeding syndrome when your patient's at risk, here are some steps that you can take. So first, initiating calories a little bit more conservatively. Instead of aiming for maybe 25 or 30 calories per kilogram, you start with 10 calories per kilogram or at least 130 grams of carbohydrate daily, since that is the daily required amount. And then you can increase by 33 percent daily until your goal calories are reached. In terms of electrolytes, you'll definitely want to check potassium, magnesium, and phosphorus before initiating nutrition. If they're low, consider checking them every 12 hours for three days and repleting per your standards of care at your institution. If electrolytes are difficult to keep within normal limits, that's when you might want to back off on nutrition advancement and take it a little bit more slowly. For vitamin supplementation, thiamine at 100 milligrams per day for seven days is recommended as that is a required co-factor in the Krebs cycle for carbohydrate metabolism. And of note, thiamine is not absorbed very well in the GI tract, so for patients at very high risk for refeeding syndrome, I would consider the IV route. And then continue thiamine for a longer period of time for patients with severe starvation, chronic alcoholism, or other high risk for deficiency. So moving on to our next question then, is this patient hemodynamically unstable? Well, there is really no evidence-based definition of hemodynamic stability, so this is going to be based on the trajectory of the patient and clinical judgment. And this remains quite a controversial topic. So our patient is on norepinephrine at 0.2 micrograms per kilogram per minute and maintaining a map of 66. So here are some recommendations that are expert opinion in terms of a way that you could approach how to feed a patient who is on vasopressors. Holding enteral nutrition at a low rate, so not advancing very aggressively, or discontinuing enteral nutrition and considering parenteral nutrition if hemodynamics are worsening, and that could mean that vasopressors are increasing, norepinephrine is greater than 0.15 mics per kilogram per minute, you have to add a second vasopressor, or serial lactate levels are greater than 4 even after treatment in patients without liver dysfunction or shock liver, and then consistently maintaining a map of less than 65. Then if and when the patient becomes hemodynamically stable, in other words those conditions are reversing, that's when you can start to increase in 10 to 20 mils an hour increments every 4 to 8 hours or as the patient tolerates to achieve your goal rate of enteral nutrition. So the reason that this topic remains so controversial is because of the potential risks of enteral nutrition in shock states or low flow states, and that includes non-inclusive bowel necrosis and non-inclusive mesenteric ischemia. These concerns are raised mostly based off of case studies, so it's important to take a look at the literature looking at larger patient populations. This 2020 review by Patel and colleagues looked at how common are non-inclusive mesenteric ischemia and non-inclusive bowel necrosis in patients who are receiving enteral nutrition while on vasopressors, and in these seven randomized control trials totaling 12,219 patients, 36 patients had these complications, which is 0.3%. In my own personal practice, I make sure to look at hemodynamic stability, looking at vasopressor doses, number of vasopressors, whether or not it's escalating or decreasing, MAP goals, lactic acid, and I make my clinical recommendations on an individual basis, knowing that the incidence is very low but also monitoring very closely for any complications. Now we'll talk about how much should we feed and how fast. So we've already talked about the importance of enteral nutrition on gut integrity and starting enteral nutrition within 24 hours if possible, otherwise within 48 hours of ICU admission, and starting lower and gradually increasing towards energy targets. You want to avoid overfeeding in the acute phase of critical illness, so increasing gradually and not exceeding 70% of energy needs in that early phase is going to be important, and then you're going to want to target 80 to 100% of resting energy expenditure after day three. Now here's where that separation in groups comes in between patients who are at high nutritional risk or who are malnourished compared with those who are low nutrition risk or not malnourished. Maybe you want to provide a hundred percent of energy needs on ICU day 4 or 5 for those who are at higher risk and target a hundred percent of energy needs by ICU day 7 for those who are lower risk or not malnourished. So what are those calorie targets? The American Guidelines recommend 20 to 35 calories per kilogram for non-obese patients, as well as 1.2 to 2 grams of protein per kilogram per day, whereas the European Guidelines suggest indirect calorimetry measurement or 25 calories per kilogram and 1.3 grams of protein per kilogram of actual body weight per day, and that would be delivered progressively. There are recommendations in the American Guidelines to adjust those calorie targets for patients who are obese, so 11 to 14 calories per kilogram for BMI between 30 and 50, 22 to 25 calories per kilogram ideal body weight for BMI over 50, and then you can see the recommendations for protein below that targeting over 2 grams per kilogram of protein for BMI 30 to 40, and then greater than, I'm sorry, 2.5 grams per kilogram of ideal body weight per day for BMI over 40. So looking a little bit closer at the protein requirements, I know everybody likes a good pocket guide, so this table was developed based on the FCCM and ASPEN 2016 Critical Care Guidelines, and you can see the various recommendations for protein needs based on category. I'm not going to go through these in detail, but please feel free to take a couple seconds and look at this in more detail. Coming back to our case patient who is severely malnourished and at high nutrition risk, the dietician estimates calorie needs at 2,000 calories per day, which is 17 calories per kilogram, and 156 grams of protein per day, which is 2 grams per kilogram ideal body weight, as this patient is on continuous renal replacement therapy and you lose amino acids through that therapy. Remember this patient is on vasopressors, but the team opted not to start parenteral nutrition, so the plan is to start enteral nutrition using the oral gastric tube that's already in place, and then you'd use 1.2 cal per ml formula, which is iso-osmolar, generally, and 25% protein at 20 mils an hour, with a plan to advance enteral nutrition when off vasopressors by 10 mils an hour every 8 hours to a goal of 70 mils an hour. This will meet calorie needs, but it will fall short a little bit on the protein needs, so most institutions are going to have a protein modular that will provide a little bit of extra calories, but especially more protein to meet those needs. So fast forward a couple days, vasopressors are off, enteral nutrition is advanced, but then the patient develops emesis on and off, and enteral nutrition is frequently held. The patient has a decline in respiratory status, develops ARDS, requiring prone positioning, and cannulated for ECMO. He's back on norepinephrine, which is at a low dose, but he's only received 25% of his estimated needs over the past three days per the tube feeding pump history, so this patient has now been underfed for six days and meets the criteria for severe acute malnutrition. Even if our patients didn't meet criteria for severe chronic malnutrition coming into the ICU, this is definitely possible if this scenario takes place for other patients as well. So the question is then how would you adjust the nutrition regimen? So most of us will start thinking about parenteral nutrition, and the general indications for parenteral nutrition are listed here, so you can take a couple seconds to look at these, but it's essentially when the GI tract is not functional or not accessible. But there is increasing focus on using parenteral nutrition when nutritional requirements can't be met orally or enterally, and also providing parenteral nutrition earlier for malnourished or high nutrition risk patients. Some of you might be familiar with the NUTRIA 2 trial, which was a multi-center randomized control trial in 44 French ICUs, and they enrolled patients who are in shock requiring mechanical ventilation and vasopressors, and of note that vasopressor median dose was 0.5 mics per kilogram per minute. These patients were randomly assigned with feeding to commence within 24 hours of mechanical ventilation with either enteral nutrition or parenteral nutrition, and you can see there are about 1,200 people in each group. These patients were targeted to have normal caloric intake between 20 and 25 calories per kilogram per day, and the primary endpoint of this randomized control trial was 28-day mortality. Looking a little bit closer at the patient population or the characteristics, these patients were about 66 years old with a mean SAPS 2 score of 59 to 61, a mean SOFA score around 11. Medical patients comprised most of these patients in both the enteral and parenteral nutrition group. Similar amount of patients in septic shock compared to other shock states, and again that median dose of norepinephrine was around 0.5 mics per kg per minute. Next, looking at the outcomes, we'll start with median days of enteral nutrition, which is not surprising. Those who received enteral nutrition did indeed receive more days of EN than those who received early PEN, but those who received PEN had a higher daily caloric intake and higher daily protein intake. But looking at the primary endpoint of 28-day mortality, there was no statistically significant difference. Those who received early enteral nutrition did have a higher incidence of bowel ischemia as well as colonic pseudoobstruction, but I think it's important to look at the median dose of norepinephrine for this population. Remember they received 0.5 mics per kilogram per minute. In terms of ICU-acquired infections, however, there was no difference between those who received early EN and early PEN, and this is one of several recent studies to show this. The others were the CALRIS trial, and there was also a meta-analysis done by Elke et al. So coming back to our case patient, on day six supplemental parenteral nutrition was started due to poor enteral nutrition intake, and they were started without lipids, which is common in my practice as well as patients who are receiving some enteral nutrition are getting lipids from that route, and a lot of patients are receiving propofol or diprovandrips. On day eight, ECMO was decannulated and the patient was taken off vasopressors. By day 10, enteral nutrition was being tolerated at 60 mls an hour for the past 24 hours with a more calorically dense formula this time, so a little bit smaller volume. Still 25% protein to meet calorie needs, but again falling a little bit short on the protein. Parenteral nutrition was discontinued because EN was meeting full calorie needs, and then an enteral protein modular was ordered but was not being given consistently. Sometimes I'll actually get the question about the enteral protein modulars. Is it really important to give those? Is protein really more important than calories? So I think it's important to come back to why protein is so important, and all of these conditions listed on this picture result in higher protein needs. This describes many of our ICU patients. We also know that acute skeletal muscle wasting and critical illness is prevalent, and in 2013, Puthikary and colleagues attempted to quantify this loss by measuring cross-sectional area of the rectus femoris muscle at days 1, 3, 5, and 10, and you can see that there is about an 18% loss in this cross-sectional area over that time. You can also see on a cellular level the difference between healthy tissue on day 1 and what that tissue looks like on day 7. In this post hoc analysis of prospective observational data of 843 ICU patients, they found that a 10 to 20 percent energy deficit decreases mortality, and energy targets were determined by using indirect calorimetry. So this is adding to the argument that energy overfeeding worsens outcomes. And then protein intakes greater than 1.2 grams per kilogram per day resulted in lower mortality. So the last study that I'll share on this topic of protein versus energy intake is this observational cohort retrospective study from 2017 looking at 2,800 mechanically ventilated patients from 202 ICUs across the world. This is coming from our International Nutrition Survey database, and they looked at the impact of greater protein intake on predicted probability of mortality, specifically between patients at high nutrition risk versus low nutrition risk. In patients at high nutrition risk, mortality was lower with each 10% intake in protein. So aside from muscle wasting and mortality, there's of course been other randomized controlled trial data looking at protein delivery and its impact on outcomes. So some of the things that we have seen was improved SOFA scores at 48 hours with increased protein delivery, not necessarily length of stay or mortality, slight reduction in mechanical ventilation time about one day over three weeks, and less fatigue, greater forearm muscle thickness, but no difference in mortality or length of stay from this third article. What I'll be interested to see from future research is the impact of protein delivery on outcomes such as functional recovery and disposition from the hospital, whether that's to home or a nursing facility or rehab. So to wrap up our case, on day 12 he was successfully extubated and the OG tube was removed with extubation of course. And after a prolonged intubation, there's always concern about functional swallow, so the patient remained NPO until swallow studied the next day when he passed with recommendations for nectrothic liquids as long as he was sitting in a chair. He was also prescribed oral nutrition supplements since he was only eating about 25 to 50 percent of meals, and yogurt with probiotics were also started. And this patient, regardless of nutrition interventions, still decreased by five kilograms and at day 16 was discharged to rehab. So to summarize this presentation, early enteral nutrition is preferred over parental nutrition due to its beneficial effect on gut barrier and immune functions. You'll want to avoid overfeeding from any calorie source in the acute phase of critical illness, but focus on meeting protein needs early. If enteral nutrition is not adequate by day 7, at the very latest, supplemental parental nutrition should be considered and earlier for patients who are at high nutrition risk or severely malnourished by day 4. And then of course, re-evaluate nutritional goals with changes in condition and as the patient approaches the recovery phase of illness. Thank you.

nutrition support

ICU

gut

enteral nutrition

complications

protein intake