move towards getting started while everybody finishes getting their drinks and getting refreshments. I just, some housekeeping things while we get started. Make sure you fill out the evaluations at the end. I hear they're very brief, so, but it's very helpful to the society. And with that, I'll introduce myself for those of you I haven't met. My name is Paul Wischmeyer, and I am a professor of anesthesiology and surgery at Duke. Where I also work on the TPN team, and of course I'm a critical care physician there. I will tell you more about my co-presenter, Krista Haynes, in a moment when she comes up to speak. So, we're here to talk about making the switch and new data for new lipids, which yay, finally, thankfully we have in the US. And we can actually talk about them for real clinical use. And I'm gonna, we're gonna tell you about, and Krista especially is gonna tell you about some exciting new data that we generated after the switch was made at Duke. So, I think to start, the first thing is it's appropriate for us at the dinner program to say, you are what you eat, right? I think that's really essential. And of course, an essential part of what makes up what we eat is the lipids. And of course, we know, unfortunately, the evolution of lipid intake in our patients and their everyday lives has not been so ideal over the years. So, what do you think the omega-6 to omega-3 ratio is in your diet? Anyone have a guess? Or in the Western diet? You don't have a guess what it is? Yeah, I hear some numbers that are pretty close to right on, so 18 to one. Anyone know what it was? You know, the Mediterranean diet is reported to be the healthiest thing for you, right? What was it in Greece 20 years ago? Two to one, good job. What do you think it is now? Yeah, not so good. We've imported, as we'll talk about, not so great foods there too. In the ideal world, what should it be? About one to one, right? And so again, we as humans have evolved away from the ideal life-preserving lipid diet that, and again, we need to be thinking about this for our patients as well, and it's gonna change the kind of patients that we're caring for because of their diet. So, lipid intake has changed in the last 100 years, and as you can see from the data I just showed you, this is not unique to the United States. We've imported our poison everywhere. You can find our bad food in all parts of the world, not just in Europe, but in Africa as well. So, this is everywhere, and it's really a problem. To give you a sense, and justing aside, to give you a sense of what a significant problem this is, there's some really interesting data coming out of India. I was in India last month, and I read a lot about their diet. I was talking about nutrition to an Indian population. It's hard to talk about protein often in that population, so I talked a lot about protein, but also lipids. So interestingly, coronary artery disease risk in rural India is quite low. They have a very low omega-6 intake in the rural parts of India, and they have a very low coronary artery disease risk. Now, within the same country, and theoretically within perhaps the same genetic makeup, the urban parts of India have the highest omega-6 intake in the world, which is interesting. I didn't know that. And their risk of coronary artery disease is three to five times higher than their fellow Indians in the rural parts of their country, so pretty dramatic. So again, you are what you eat, and I think you should be afraid of what your patients are eating, even in the hospitals. And there was one of these in the hospital I was a resident in at Denver Health back in the day. We had a McDonald's, and we'd have McMuffins in the morning post-call, too. So again, it makes you wonder, are our patients coming in an immune-dysregulated state? Of course, we have to mount an immune response when we are septic or infected, but the unfortunate part is septic shock, of course, is too much inflammation, likely, that ultimately probably becomes hypoinflammatory, but initially, it's a hyperinflammatory state. It's a top 10 cause of death now in the world. It's rapidly rising. We have the mortality from heart disease, but sepsis is rapidly rising as a cause of death. So if we're gonna put out the fire, it's gonna be harder to do in patients that come eating this, which unfortunately is way too common. And so is the fire harder to put out than before, and can we do something about it once they come to us? And so what about lipids? Is there a best choice for our patients? I think before we get to TPN and IV lipids, which is, I know, what you're here to hear about, I think first, I wanna get something out of the way. I heard there were some round tables going on where it was still being reported that TPN was a cause of infection. I wanna be sure no one thinks that's the case. I know people in this room are pretty educated and dope, but here we have large trials and journals you've heard of, and thousands of ICU patients. It's just as safe to put TPN through a central line as a saline through a central line. So again, don't let anyone tell you that TPN has any relationship to infection and critical illness. It doesn't. Why is that, right? Well, we do a lot of things better than we used to. We don't hyperalimentate. When I was a kid on TPN, I was getting a lot of calories I didn't need. We control hyperglycemia. Almost all the trials that show infectious risk didn't control for hyperglycemia. We give more protein. We have a central line checklist, and we have better lipids. So again, I think this is important, and I think this is showing in our guidelines, right? The asthma guidelines have now come out and said it's just as safe to start PN or EN in your patients. A major progression forward from our previous asthma and SCCM guidelines that really says either is acceptable and equally safe to start for your patients. So there's no reason in that person that you're having trouble feeding that at any point that you need to, if you've tried intra-feeding, you shouldn't be starting PN. And I think in opposition to the idea of TPN's relationship to infection, this really critical trial was recently published in JAMA Surgery, one of the highest impact factor surgery journals in the world, that looked at the use of supplemental PN in major surgery patients, and they randomized them to an early supplemental PN strategy or a late supplemental PN strategy, and they saw significant reductions in infection in the surgery patients who got early SPN. So I think we've really turned a major corner. And why might that be, right? I mean, perhaps it's all these things, but perhaps it's also this. And finally, we have access to this. How many of you are using a new mixed lipid in your ICUs today? Raise your hands. Ooh, not very many. How many of you only have soy lipids still, or intra-lipid? More than half the room. So when I've done some pre-course surveys at big SCCM events, I gave some talks during COVID that had 1,000 people at them, large dietitians, who would know what their hospitals were using. And I would say 60% of people at those talks are still using only soy lipid. I hope that changes after tonight. So are lipids important in sick patients? Well, they are. In a 60-year-old patient with sepsis and pneumonia, what's the preferred substrate of most of the cells in that patient? Is it glucose? Is it fatty acids? Is it protein? Is it ketones? Or is it glutamine? What are most of the cells in the body using? Anyone know? None of the dietitians in the room know. Ooh, it's gonna pop up again. It's long-chain fatty acids. So lipids are really critical. So lipid is the fuel source for most of your organs, whether you're sick or whether you're at rest, right? When your muscle's at rest, it's predominantly using lipid. If you're running a marathon or an ultra, you're using mostly lipid. If you're Usain Bolt, you use glucose. But not so many other athletes, actually. Most are using lipid. Heart, it's largely a lipid utilizer under most circumstances. Liver, also, once it depletes its glycogen, largely a lipid utilizer. Kidneys, not so much. They use glucose and some amino acids that make some glucose. The brain, not gonna use so much lipid. It's a glucose utilizer as well, ketones as well. Your red cells, they have to use glucose. They can't do a lot of the metabolism other cells can do. And then our immune cells, glucose and amino acids. That's where your amino acids become very important. But lipid is the fuel source for most of the organs in your body. You can see that if you look at the different things that are being used, a large percentage of the body's functioning on lipid. And the body's challenged to use glucose in critical illness. This is old seminal data that shows as patient sepsis score goes up, that they're more severely septic, their glucose utilization goes down. And they're largely utilizing fat. It goes up actually. Now, we're still learning about this topic and Zuden Punyachary is showing us some neat data around this, but this is the traditional longstanding physiology. So this is really important for your patients to get lipid. So is there a best choice for our patients? And what does the data say? I think there shouldn't be choices, there should be data, right? And so lipid emulsions, there's similar effects from energy, essential fatty acids. They do basically the same thing when it comes to these basic tenants. But they have very different effects on your immune system and many other parts of the stress-related pathways our body faces when we're critically ill. Many different effects. And so we actually now thankfully have quite a few lipid emulsions available in the US. We have lipids that are mixed with fish oil. We have lipids that are mixed with olive oil. We have a whole range of lipids, thankfully. It's, I think, thankful to a lot of people. Some in this room who did a lot of work with Aspen and other groups to get them over here. And is this important in illness? And I'll show you that it is. They have different effects on the immune system, so it's likely important. You can see from a pro-inflammatory lipid like the omega-6 lipids, the intralipids, all the way across to fish oil and the olive oils and the others, there's quite a range of immune effects of lipids. And so, of course, the omega-6, the Big Mac and fries down the IV tubing is probably less than ideal for our patients. And that's what half the room looks like still, sadly, is using and I got for most of the years of my life I was on TPN. But now we have a different lipid we can use. And in some cases, this is an omega-3 based lipid or omega-3 based mixed lipid. And how does that affect immune signaling or inflammatory signaling? Again, if we're using an intralipid, sort of the Big Mac and fries down the IV tubing, this promotes the inflammatory response, the NF-kappa B response, the cytokine response. And it does that by intercalating into the cell membranes of our immune cells and other cells and promoting that inflammatory response, which ultimately we think promotes organ failure and the adverse effects ultimately of what happens to our patients. Alternatively, fish oil, for instance, will also integrate into the cell membranes of our cells. And it actually attenuates that inflammatory response, doesn't necessarily block it. We don't give pure fish oil to our sickest patients, but it attenuates that response is the hypothesis and does some other important things. But one of the key things we think it does is attenuate the inflammatory response. Now, there are critical things that omega-3 lipids do uniquely that are truly unique in our patients' recovery from inflammation. And it's likely Charles Surgan will win the Nobel Prize for the resolvins. But omega-3 lipids, why they're so critical to our diet, lead to resolvins, which help resolve inflammation when our body's markedly inflamed, the way we recover is generation of resolvins. And so we can either go down sort of the acute inflammatory organ failure pathways if we don't have these resolvins and other key molecules, protectins and others, or we can go down and be able to generate the things that allow us to resolve that inflammation, prevent hopefully the organ failure. So what are the key effects of the lipids we have available to us now? Clearly, pure omega-6 lipids like this are immunosuppressive. They are hard on the lymphocyte. Really, you have better choices. Nobody should get them unless you have a bupivacaine overdose. Maybe if you have a fish allergy, olive oil allergy, that's the only people I could ever imagine giving these to ever again, ever. And why is that? Well, there's years worth of data to show they cause lymphocyte suppression. They suppress lymphocyte proliferation. They impair natural killer cell activity. They do a lot of negative things. And all of you should be thinking, God, isn't propofol in that lipid too? It is. So again, that propofol you're giving has this same potentially negative effect as well as being a mitochondrial toxin itself as the drug. And a lot of this goes back. And the reason for many years, those of you who are a little older remember, we didn't give lipids but once a week in the ICU for a long time because of this concern. All we had available to us was this lipid. And this study drove the SECM asthma guidelines for many years, the only study that drove it. But it was a trauma trial that randomized people to TPN with lipid to TPN without lipid. And it showed some fairly, and a small trial, mind you, but it's concerning adverse effects. Longer length of stay, greater infections, more complications, some neat basic science was done that showed impaired natural killer cell activity and other key immune cell function was impaired in patients now, not just in the lab, by the presence of the use of intralipid or omega-6 lipid. So really, it does some pretty unpleasant things to our immune system. Those things can be seen clinically, at least in small trials. I would advocate there's nobody who should get this unless you're allergic to one of the new lipids or you have a local anesthetic overdose. That's really only people we give it to at Duke. What about the mixed fish oil lipids? We'll talk about these. This is what we're here to talk about the new data for. In short, is this a more ideal lipid? And going back to sort of retrospective and observational data, there were signals that there were benefits to patients who were receiving a lipid that had some fish oil in its mixture. Again, not necessarily pure fish oil. Most of these studies were done with mixed lipids that contain other lipid content as well. It really spares soil. You can think part of the goal is to give some of the benefits of fish oil, but a big part of the goal is to not give so much omega-6 Big Mac and fries down the IV tubing. And so this was actually, I was the reviewer for this paper and wrote an editorial on it. It was submitted to Critical Care Medicine a number of years ago now. It used an olive oil-soil combination and they looked at infectious complications as a primary endpoint and they saw significant reductions in infection. This was a nicely done randomized controlled trial published in Critical Care Medicine. Didn't have an effect on mortality, had a trend towards reduced length of stay, but infection was really the endpoint all of us imagined we would see an effect on, given the impact of lipid and fish oil versus soil on the immune system. And we saw that. Now, many, many trials have been done since then. 2019 updated Pradelli meta-analysis looking at fish oil containing lipids, not pure fish oil again in most cases, 49 trials, many in the ICU, many in surgery, 3,600 patients have been studied, showed a 40% reduction in infections overall. So again, this is many, many trials now showing this effect. Reduced length of stay in the ICU by about two days, hospital length of stay by about four days. So significant benefits, 56% reduction in sepsis episodes in these patients. Again, these are thousands of patients studied, numerous trials. This is sort of the summary of the data. I think this is a paper that's worth reading and I would encourage you to do that. The other good thing is they reduce costs and there's lots of cost-related data around the world, not just in the US, showing that the use of mixed lipids reduce cost in patients who receive them. So that's good for your hospital. Again, these lipids don't cost much more, at least in our hospital, they don't cost much more, maybe a few dollars a bag, but the cost savings potential is really significant for your patients. And that's a good way to help get it through PNT, which is a challenge I hear a lot of people have. And so the cost differences in a lot of these trials, especially in the US, show pretty significant differences in cost. And we think a lot of this is because this has a much more neutral impact on the immune system. It doesn't have the immunosuppressive effects of the soy lipid, which hopefully will be abandoning soon. And again, the recommendations from the Lipid Summit that was had a few years ago, we had another one just a few months ago. You tell the recommendations will look stronger in a few months when this comes out, but we recommend using lipids that contain omega-3 fatty acids. It was an expert panel of people around the world. We just have had another of expert folks and the recommendations will be the same, that fish oil-based lipids are really where we should be headed for the care of our patients. And I think that's really critical. So what about the other complications that lipids or TPN can carry, right? We know liver disease is an issue and you'll hear about patients that have this. What is it about lipids that cause that? Anyone know of the things you see on the screen? What causes the parental nutrition associated liver disease? What's the phytosterol content of the lipid? So this is another key thing that the newer lipids have reduced and that is better for our patients. So can PN lipid choice reduce liver injury? And again, this is a big problem. If anyone who's on TPN for any length of time or was very sick is at great risk for this. And we used to see it a lot. So we would spare or not be able to give lipids to our patients. And so it's cholestasis, right? It's the bilirubin pathway is disturbed. It's associated with longer PN administration being septic like many of our patients are. And again, overfeeding of soy or glucose because the phytosterol content in soy lipid is high. So again, lots of issues with this and hepatic phytosterols are a big part of that. So there's very high levels in soy lipid. And that was one of the reasons a lot of times we had to not be able to give lipid. And so you can see the newer lipids, the mixed lipids that have fish oil that we're gonna talk to about when we use at Duke has significantly less phytosterol content. And the data from a number of trials now show reduced liver injury, especially over time in the patients who receive them. And we're gonna talk about that in our data from Duke. And Krista is gonna tell you about that in a minute. But liver function parameters and other studies have been improved by the use of a mixed fish oil lipid versus a soy lipid. In fact, we almost never see, I can't think of the last patient we've seen any kind of biliary cholestasis from TPN at Duke in the last few years. And I'll talk to you about some very meaningful experience we have with that. So again, the recommendations going back all the way to 2013 from the Canadians, again, are that we should be using lipids that reduce or eliminate, spare, reduce is the better word, spare soy lipid administration. So we should be giving less soy and more of the other neutral or inflammatory reducing lipids like fish oil and olive oil. And so again, avoid pure omega-6. And this goes all the way back to almost 10 years ago now. Aspen guidelines say the same, the use of soy soybean oil should be avoided due to pro-inflammatory effects. I think Aspen is the most pragmatic of the guidelines. And I think very recently has addressed this topic really nicely. We shouldn't be using them anymore and our colleagues overseas really don't. And so I think this is something we in the US need to embrace. And there's no reason to delay giving lipids because we have better choices now. We don't have to avoid lipids in our patients, but we have to avoid the omega-6. This is one last trial that shows that really any other lipid other than a soy oil lipid leads to better outcomes. So again, the use of official containing lipid improved outcomes pretty remarkably across these groups of patients as published in Critical Care Medicine a number of years ago. Really, you could say anything you give besides soy, your patient's going to do better. So do I practice what I preach? I do. At Duke, we switched to a mixed lipid in really the minute we had the chance to do it in May of 2017. We pushed it through our P&T. It passed on the first try. It was very easy to pass. And we switched everybody on one day, which is what the data you're going to hear from Chris is about. In fact, almost all our pediatric patients, we are switched as well. And you're going to hear pediatric data as well. So as I finish, why am I so passionate? Why would an intensive care doctor spend 25 years of their career studying nutrition? And why do I hope you care and change the lipid your patients are receiving too? Well, again, Derek Angus has taught us. He's the editor-in-chief for JAMA's Critical Care section that all of us will be in the ICU at least 1.7 times in our lifetime. So don't use your admissions up too soon. So someday this will be you or someone you love. And likely for many of you, it already has been someone you love. And so again, this is very personal for many people. And as some of you may know, I've used up a lot of your ICU admissions, so maybe you'll avoid it because from a young age, this has been me. This was me on TPN at age 15. I had inflammatory bowel disease, was diagnosed as a 15-year-old, spent a year on TPN, my colon perforated. I was in the ICU for a prolonged period of time, had an ileal pouch surgery that failed, and now 27 abdominal surgeries later, I'm short gut. I have 140 centimeters total bowel, no ileum, no colon. And so TPN is a big part of my life. In 2014, I got, of course, with me. Now they tell you when you have IBD and you have your colon out, you're cured, but you're not, especially if your colon leaks and you need a toxin-made colon, you get adhesions and you get bowel obstructions. In fact, sometimes you get them four or five times a year, even when you try to eat the right things. And many physicians don't know anything about eating the right things, and so they get very sick and they don't know why. So that was a big part of my life. and in 2014 I got obstructed and this was me in my own emergency room at University of Colorado when I was there being taken care of by my own residents with a lactate of 10 being rushed to the OR with a severe bowel obstruction and acute abdomen. I spent 23 days on PN during that hospitalization almost 10 years ago now not quite actually wrote my own TPN with my dietitians I was the director of the TPN service thought I'm pretty healthy pretty fit 25 kcals per kilogram and half per kilo per day of protein ought to do it right yeah but I had troubles I had polystasis myself it limited me giving really more calories over my stay because we didn't have the new lipids yet and I went from looking like this with my son at my grandfather's house probably the best shape of my life to looking like this in 17 days I lost 20 kilos in 17 days a kilo a day on TPN I couldn't even walk down the hospital hallway in a week because I was too short of breath I went from running five six miles a day to not being able to go five six yards without feeling short of breath I see card weakness is real and no one's immune right at least I thought no one was couldn't even pick up my own child five months later at Christmas and he wasn't that big he's a lot bigger now but he wasn't so big then and and so that was really frustrating what did it take to recover took two years and 4,000 calories a day remember that number we're gonna come back to it two grams per kilo per day of protein and I like to show pictures of me with my ostomy I have a lot of ostomy patients at Duke and a lot of them tell me their lives are over they'd never gonna be able to do anything again because they have this ostomy and I say there's nothing you could do before that you can't do with an ostomy and I always hope this gives them some hope plus they always look at me and say there's no way you have an ostomy and I always say no you can do this too so patient recovery is very personal for me because I knew even in 2014 and I'd always tell my residents this it's that nightmare dominant that you don't want to see in the ED and that might be me someday and I knew I'd be in the hour on the ICU again and in 2022 as my wife who's sitting in the front row knows well we were out of town and I got obstructed in Hawaii where they don't allow visitors and it was really terrifying and it made us afraid to leave and so I got with Deb Sudan who's our intestinal transplant surgeon at Duke and I said I need to have an elective operation I can't live this way I can't live being afraid to leave town because I only trust you to operate on me and so I thought boy this is gonna be a big surgery she's like probably 12-14 hours Paul is what I think if I can not have you lose any more bowel we'll see and so I thought gosh I'm gonna lose all this weight again I'm lose all this strength again I'm gonna spend years recovering I'm even older now it's gonna be rough so I went to surgery 13 hour surgery lost 20 more centimeters of bowel unfortunately my bowel was adhesed to my ureter and to my gallbladder and so she took all that and lost some more bowel in the process admitted to my own sick you this is me a few hours after surgery my wife took this picture and started TPN within 48 hours because we knew I'd have an ileus we knew it would be bad this is me walking with my TPN around my ICU where I work every day unfortunately two days later I woke at 2 in the morning gown soaking wet and and looked down on their stool pouring from my incision and I get rushed back to surgery it was it was terrifying and I was had a fever and don't have a great memory unfortunately my family does and ended up with two emergent surgeries they couldn't fix the hole and my greatest fear is all of us who carry your fish to patients are is getting a fistula right sometimes they don't heal for years so that's what I saw I was back this is me intubated in my ICU being cared for by my nurses and residents and fellow ICU attendings sickest I've ever been in my life had a persistent GI fistula and I thought oh boy as I woke up from this I'm like that's just gonna take years to recover from maybe I'll never recover some of the data says right I'll never be the same I'm gonna lose all this weight I'm lose all this strength maybe not can we do things differently we've done before and I would have never said this I've been teaching for 25 years you can't avoid the weight loss you can't avoid the weakness I couldn't and if I couldn't I thought who can so we did some things differently we started TPN early first right and we personalized it with indirect calimetry I knew going in this is that was me getting indirect calimetry two days after surgery that my resting energy expenditure is 3,000 calories has been for years it was after surgery as well I was walking a lot I was very active after my surgery even in the ICU so my dietitians and I thought let's add 1.2 to 1.3 was that leave us with 4,000 calories a day nobody wanted to write that TPN but I said you got to do it 4,000 calories a day small lipid 2 grams per kilo per day of protein this is me wandering around the IC with that that concoction running I was discharged home on that for months 4,000 a day because that's what it seemed like I needed lipid choice matters I had no LFT abnormalities on 4,000 calories a day for months this is our tiny dog who helps coach me and of course rehab has to be part of it this is me with my fissile drain my open abdomen and my PICC line and my TPN exercising on our Peloton Peloton's the greatest invention of all time I don't know why we don't use it more for our patients and you'll hear my wife in a minute but but we realized that we can do this and and the reality is I lost less than five kilos the entire time being that sick I lost 10 pounds maybe kept looking in the mirror why is it my face getting thinner never did never got I never lost weight I was back to my pre-op weight days after getting home on TPN still didn't eight weeks after surgery I said Deb I want to dance and dance competition my wife and I'm gonna lift her over my head five times and she's like you can't lift more than 10 pounds for eight weeks eight weeks and one day I said can I start picking her up she said do you think you're strong enough I said I think I am weeks eight weeks after my last operation so I didn't lose any strength so it's not mandatory I still sometimes I'm not so sure I believe it but it isn't because we have better care we can personalize what we do we have better lipids lipid choice matters it saved my health and my ability to function in the world I probably wouldn't be here without it right now yet I wouldn't be well enough to be here this is why I'm passionate this is why I think it matters that you switch and that you care which lipid you're giving to your patients probably something it's an afterthought for most of you on rounds I'm not the dieticians thankfully but this is why I care about this and I know you care about it or you wouldn't be here tonight right that's why you're here so again we have to do better the way we feed patients has to change it should never be the same and if we're gonna create survivors of our patients and not victims we have to remember our patients and we are what we eat and what they get and what they get in their TPN and what they eat matters and so if you're still using intralipid please stop from personal experience and from hopefully the data I showed you your patients deserve better there's no way I could have pulled that off without this this summer use a new lipid I really don't care which one but get a different one get a different one I hope the data is compelling that we share you tonight but but lipid choice matters in adults and I'm going to show you Chris is going to show you actually in kids as well and lots of us aren't using them in this room reinforces to me that we have a long way to go and so we need better education and we need consistent adoption we have the chance we fought for years to get these new lipids in the US 20 years of my career we fought for this now we have them so we need data right we continue to need data I think our guidelines will reflect when we get better data our guidelines will be more firm on this and that's where I'm excited to have probably the most talented and and really probably going to be the most successful trainee I've ever trained Krista Haynes come up she's a superstar nutrition I'm sure will far surpass my accomplishments by a long way and not too many years but but she's going to tell you about well hopefully we can take patients like this have them looking like this and then have them leave like this or at least like this and so I also want to encourage since you're care enough to be here tonight we've started a new Duke nutrition clinical fellowship it's an online fellowship it has 25 modules with the best people from around the world teaching the classes on all different forms of adult and pediatric nutrition it's very inexpensive physicians dieticians pharmacists nurses anyone can take this class a PPS we're running our first year of the fellowship right now we'd hope to get five physician trainees we have 12 this year the models only take 15 to 20 from four continents seven countries and so we're really excited but we have people from all around the world in this and I encourage you to keep on social media and watch us we'll be offering new classes and new modules soon so with that I'm going to leave it to Krista to tell you about the exciting new data and listen because this is the most talented young nutrition person I know in the country today and so I'm gonna leave it to her thanks Krista can you guys hear me hey guys so how do you follow that I mean that's amazing with tables so hopefully a lot of you have seen that we published a new paper where we took the lipid emulsion changed it as he told you over one day this is on the adult data so we went from amazingly enough soy lipid emulsion to a mixed lipid emulsion and change the entire hospital system in one day and it worked and so we decided to take a look at that data obviously the study was funded by FK so just to let you guys know that but we went back and we pulled all of our data on pre and post change so as he said we changed in May of 2017 and we wanted to look at this data so we did one year pre switch and two years post switch the nice thing about this study is that we're at one institution there by all of the caregivers providers nutritionist dietitians are all the same so we didn't change a lot of the care we just changed the lipid our population overall in the adults was 1,200 people greater than 18 years of age our pre sample size change was 341 patients and our post was 859 our primary outcome was hospital length of stay because we've seen that to be important in previous studies and we had some amazing statisticians look at this data so you can look here's the baseline characteristics on all patients I'm going to also show you some data on just the ICU patients and as he alluded to the pediatric patients that isn't published yet but you can see our mixed lipid group was a little bit older here you can see that our pre change group had a little more chronic disease but then our post lipid change group did have more ICU admissions they're more chronically ill patients so then we wanted to look at obviously liver function tests because that's everybody's biggest fear another thing to let you guys know for this data analysis when we did this switch I know a lot of you use soy lipids and you don't give them every day once we switched we give this lipid every day so here you can see we do a daily lipid dosage just looking at day amounts because this is a data where we get 24 hour points you can see that our data lipid dosage was no different per day for both groups so here's length of stay for all patients so this is our ICU and non ICU adult TPN patients so everybody admitted to the hospital here we're looking at our length of stay which was our primary outcome which we did have a significant finding for the change so then let's take this down to just the ICU patients or smaller population looking at our most critically ill patients here I want to focus in on liver disease itself so you can see in our priests change group for comorbidities we had less liver patients than we had in the post so this is a liver disease prior to actually starting the lipid itself you can see also we have chronic disease here renal failure for a post lipid change group they were actually sicker and then for our ED admissions so telling us that our emergent cases versus not our post change group where we gave them the mixed lipid a huge majority of those were emergent so obviously they're sicker they didn't have any prehab planning they didn't get to do any of the things that he gets to do before surgery so we have a sicker group in the in the post lipid change group so now let's once again look at LFTs but look at LFTs in our ICU core cohort and again let's focus in on the lipid daily dosage and you can see that in the post change group we did have a significant difference in how much we were actually able to deliver and so we were delivering more of the lipid kind of like I was talking about we can do it every day and then once again we want to look at our LFTs and despite the fact that we were delivering more lipids to these patients we did not get a rise in total bilirubin it actually decreased which is what we're always looking for and worrying about so now let's look at infection costs he's already proven to you or hopefully at least showing you that there's a bunch of data out there that shows we don't increase ICU infection using TPN so now we're going to look at hospital length of stay and then incidence of UTI so once again length of stay we were able to reduce it by using a switched mixed lipid emulsion and then our UTI rates actually decreased so I think a lot of others of these trended towards significance so if we had a much bigger population than just one University which hopefully we're going to be able to show you in the future that would be significant as well and then once again our 30-day readmission on both groups there was no significant difference but it kind of trended to so big picture we decreased length of stay by approximately five days by switching so this is the paper that we keep referring to that was just published in critical care medicine on the adults and in conclusion with these 12,000 patients or 1,200 patients it reduces hospital length of stay and that's in unadjusted analysis and then it also improves outcomes so here's our 447 ICU patients and you can see it reduces hospital length of stay even in the sickest group by approximately five days what else does it do it reduces ICU length of stay so it reduces our infections it reduces our and it reduces our infections and then also we don't see any rise in our t-billy so for adults we recommend obviously switching to in this study we did a four oil mixed lipid emulsion as you know but any mixed lipid emulsion that's not just a single soy lipid will reduce your complications hopefully it will reduce your length of stay it decreased the hepatic dysfunction that we worry about even though we delivered more fat and it was in a sicker population so I keep harping on it but I think we need more data and bigger populations and then we'll see even more consistent improvement in the lipid data for these patients and we especially need data to be able to advance TPN in peds and the pediatric ICU so let's talk about kids so we did the same thing on kids even though I know this wasn't actually approved here until recently which is very exciting for us we were able to implement this to our entire pediatric population in May of 2017 we did the same retrospective study looking at one year and pre in two years post and critically ill patients we didn't want to do the super baby so we did one month to 17 years old so just straight pediatrics and what we had 612 patients in this group and the pre change group was 207 post change 478 so we obviously had more patients but it was two years of data primary outcome once again was length of stay and then overall infection risk so here is our baseline characteristics for all the pediatric patients we were able to switch you can see the total numbers as well as our pre and post switch and you can see that the post switch once again is a sicker population they have comorbidities including congestive heart failure and cancer and then also you can see that the higher rates of ICU admission mechanical ventilation in the post switch group so obviously you would think we're going to have worse outcomes in those groups unadjusted outcomes looking at these so this is our non control non non controlled for data you can see that we have 90-day readmissions is trending towards significant it's not significant but in the internet are in the post switch group so here now we're looking at the length of stay for these patients and you can see here that the length of stay for the post switch group once we're controlling for all the comorbidities so this is our regression analysis controlling for all of those comorbidities age everything else that our length of stay was significantly decreased and also our UTI rates so our infection risk as we were looking at before so you know family decreased now we're going to focus in on the pediatric ICU patients so our sickest population here you can see that both groups were equivalent there's no significant differences between the two groups that we were looking at I know you love my tables and then so here we're going to look at LFT numbers so in our pediatric ICU patients using crude numbers looking at bilirubin where we think and and bilirubin impedes is even more significant going up usually you can see that during our post switch group our ALKFOS our total bilirubin and our ALT all had a Delta Delta decrease in our post small switch group so now once again crude numbers so this is non-controlled we're going to look at length of stay in our pediatric patients and then 90-day readmissions what did we do we decrease length of stay by 13.1 days and we decreased overall hospital length of stay for the other group for four days finally looking at the pediatric ICU patients doing our controlled analysis here's our 30-day readmissions and our 90-day readmissions you can see those are there's no difference in actual readmission rates but once again our length of stay is decreased and so is our UTI rates so lots of tables lots of numbers but here's our key results when we put mixed emulsions in kids we get significantly decreased LFTs we get significantly decreased T bilirubin so things we're looking at we get to decrease infection and our readmission rates are trending towards improvement with the mixed lipid emulsion group so once again changing to a mixed lipid emulsion is going to approximately give you a 13-day reduction in unadjusted data length of stay and when you start adjusting for all comorbidities we're still having a reduced length of stay so as as Paul has said many times and I completely agree with him and I hope this data kind of proves it to you that we should probably not be giving people just a basic single soy-based lipid because we're not helping our patients out as you can see here with this data. So if we can decrease their time in the hospital and we can make them do better and we can give them more fat and keep them stronger and have better outcomes, then this is the way I think we should be moving. So what do we need here now? We need better education. I know a lot of people, despite the fact that we're using these mixed lipid emulsions even in our hospital system stopped our TPN. We'll have a super sick patient. Somebody will round, they'll see the patient. They'll be like, oh my God, their LFTs are going up and they'll stop the TPN and like three days later somebody will realize the TPN is being stopped. So we've been starving this patient for four days. And then we get a call finally four or five days later and we restart it and try to explain to them, hey, we're using a different TPN and they have no idea. So I think one of the biggest things is not only, I mean, I was preaching to the choir in here. Everybody knows what I'm talking about. But you walk around your hospital, nobody knows which lipid they're on, much less that we have new lipids that are actually good for us in certain ways. So consistent adoption of the new lipids and then more US data. So people actually will listen and push this forward. So lipid choice matters. It improves outcomes. It allows us to get more calories and more fat in our patients. I think it's better. I got to watch Paul get better on it and help take care of him, which I thought was amazing. And so if you're still using soy in your hospital, please stop. We don't care which one you use. So thank you guys so much. Now we're up here if you guys have questions, yeah I think there's a microphone around the room. Please feel free to ask questions and we'll Please Special prevention is for a urinary tract infection It's a really good question, what do you think about UTI? Why was UTI the one outcome that really changed? Um, I I have I don't know why to be honest with you We did look at all infection risks and even with pneumonia. They were all trending towards significant I think that's the only one we actually got to significance. I think we had better bigger data sets It would be all cause infection to be honest Yeah, no, it's a good question. I'm surprised it was consistent, right? It was consistent across multiple ICUs multiple, right You could say maybe one ICU changed how they did catheter related care, but this was across the kids This was across the adults and I think one of the things I think Krista said it Well, that's really compelling about this to our knowledge This is the first pediatric ICU data ever for a lipid comparison in any pediatric setting critical care setting There's some in neonates, but there's none in the pediatric setting But it was very consistent across all the ICUs in our hospital and just FYI I like most studies. I think when you're looking at two populations, they'll do all of the analysis together we didn't we did all of the adult analysis together and then we Decided to go do the PEDS afterwards and then we did the PEDS analysis and still came out with the same results And she didn't show the slide but I think the next thing we're going to do and Krista's leading this charge is we're gonna we're we're gonna tap the premier database and We're gonna look at 10 million adult ICU patients and we can see a substantial number. They got some off Substantial number they're getting interlipid and this is real-time data, right? That'll be concurrent use data So we're excited to tap some of the large US databases We could resolve who gets some off and we can resolve who gets interlipid And so in real time we can see in real time patients concurrently cared for Are we seeing differences? So that's one of the next things we're going to do Two more questions have one in the NICU as one question You know approved to use in the NICU and the other question is that for a lipophilic drug toxicity You know, sometimes we get teenagers that you know, they ingest, you know beta blockers or are some antidepressants are We have order lipids or this type of a small works also. No No data We don't know if it does We could ask that local anesthetic question as well Theoretically But I wouldn't even speculate and I wouldn't risk it we always have the other in the hospital It's that's the really only place we use it fish out of fish physiologies I'm the NICU We have data for the NICU. We have not we have not published it yet It did show length of stay reductions like we saw in the other units and in some other But we just that's one of the next things we're gonna do because we do have data there and they made the switch as well Yes, yes Yeah the whole hospital So, I don't know ever, you know, a lot of you probably outsource your PN at Duke. We're big enough We compound in-house We have a we have a sterile compounding room and Duke has for many many years and there are pharmacies excellent at it But you can only run one lipid on the compound or meaningfully, right you go go switching back and forth That would be a huge infection risk. And so some of it was yes We didn't want any patients getting inter lipid anymore But two it wasn't practical really for us to give another lipid either and so it actually made the switch much smoother Although I will tell you our pede side Free hangs they do two-in-one and the lipids free so they had the option of not switching So we have some concomitant care in that pediatric population There is there is potentially some concomitant care that happens there because they don't compound three and ones on the pediatric side No, we pull the lipid. Yeah. So we pull the lipid if they're getting, but they're evaluated every day twice a day or so. Yeah. I mean, once the propofol comes to a certain level, the dieticians switch. Krista's on our TPN team as well. And so we switch to put lipids back in once the propofol comes down. But when people are on significant amounts of propofol, which we try to stop, and I hope all of you do too, we know it's a mitochondrial toxin, we know it causes ICU cord weakness, we know it impairs TCA or electron transport chain function. Propofol was never meant to be given in the ICU. It's an anesthetic drug that was meant to be given in the operating room for short periods of time. Those of you in pediatrics say, why the heck are you giving propofol? It's black boxed in the PICU because it led to the significant numbers of deaths of children years ago when I was a resident, that was black boxed in kids. That's because the people who suffer PRIS and the complications, people with more muscle mass, people with higher metabolic rates, males, people with sepsis, people with seizures, kids of course have the highest metabolic rate and so they were dying at large numbers getting propofol. It's hurting your adults too, it's just causing muscle injury and ICU cord weakness. So again, if you're going to give it more than 48 hours, find something different. We take it out of the TPN to get to your question. So Kiran from Columbus, Ohio. So I'm the medical ICU side and I always advocate early TPN if I'm anticipating somebody not to get any food for three, four days. So my surgical colleagues, SICU folks, they always wait for five to seven days after bowel surgery for bowel function to return. What's your take on that and how do you practice it? So we actually, a couple of years ago, started promoting earlier TPN in our institution to the point that we actually got some prospective data and Paul and I and Suresh Agarwal in the back just got a big DOD funded grant for a randomized controlled trial to do early versus late TPN. So we're trying to give it within 72 hours. And we pretty much universally do in our surgical ICU. Anybody with an open abdomen, anybody with major surgery, in fact most of our surgical colleagues are wonderful. They actually call us and say, why haven't you started TPN yet? If it's been 48 hours and we haven't started, we get phone calls. So it changed. I mean, Krista really drove this. She spent a lot of hours in the hospital really enrolling patients in some of the observational trials that we're doing and really helping reach a lot of our surgery colleagues and helping them work with us to look at the data and to look at the outcomes and really because of her work. Now our surgery colleagues come to us and say, it's been two days, why aren't you starting? Is something wrong? Is there something we're missing? And so it took a lot of work, but she did it on the ground and that culture changed. It was amazing to watch for me. I mean, obviously it's not 100% buy-in, but it's going great. It's pretty close. It's impressive. I was blown away. Thank you for your work. Can you talk about some of the barriers, why it took so long to be able to come to the United States when it was being used overseas? Yeah, unfortunately, and Jay Patel was in the room a minute ago. He knows this story well too. So one of the challenges for nutrition and Fresenius in the back will know this well and all the other companies, Baxter and the others alike, same challenges. The FDA has been requiring the same standard for the lipids and a lot of the TPN components that they would hold for a new drug, right? Again, they want US studies of a lipid that's been used in Europe and in remote parts of Africa for 20 years, right? And somehow we in the US are so different that we need the same studies that we've got 20 years worth of data on. The profit margins on these old, unpatented drugs are not large enough to support those kinds of research. And luckily Fresenius and other companies have invested in enough research to satisfy the FDA to finally have them come to the US. And it's been a big lift for all the companies that have brought new lipids. And so we owe them a debt of gratitude because this is not a money winner for them to go to the FDA with these drugs. That's also why we run out of micronutrients and trace elements and all the other things that you as dieticians and perhaps you as intensivists know we've been short of in the last few years is that, again, the FDA is requiring studies, new studies, of US patients for pennies on the ampule kinds of drugs that there's no way they could ever support. And so when we run out and we watch people at home suffer and sometimes die because they don't get trace elements or micronutrients and patients are dying, we think, are having complications because they're not getting the right lipid. We plead all the time at the FDA during COVID. We had numerous shortages meetings with Aspen and other people meeting with them trying to change this. And we found a pathway when we had amino acid shortages years ago and we got some approvals to bring European products over only in areas of shortage. And so we're trying to do that for other things as well. But I think the companies have really succeeded in the face of great adversity. And we have lobbied hard, although I don't know that we're really the reason the FDA listened. I think a lot of the companies were able to satisfy some of the requirements, but that's the reason. And it's unfortunate. In remote parts of Africa, they've had these lipids 20, 30 years longer than we have. And in third world regions, it's unbelievable, right, that we couldn't get them until just a few years ago. This was a huge opportunity for all of us. Improving or maintaining muscle mass, have you seen any benefit in terms of reduction in pressure injuries? So we haven't looked at pressure injuries. That's a great question. Yeah. Our new outcomes for the future studies are all functional measures, like six minute walk instead of looking at length of stay and infection risks. We're also following those too. But no, we haven't actually looked at that. That's a great point to add. You're right. Because especially in the long stairs, that's a major issue, right? A major complication. And theoretically, better nutrition, we know, leads to less pressure ulcers. So one of the real drives of better nutrition in the whole hospital setting, right, is to reduce those kinds of injuries. So that's a great end point, actually. We should have that be an easy thing to collect, right? We all rigorously collect those in all our hospitals and all our ICUs. It'd be easy data to get. We probably could get it for our Duke data, actually, if we wanted to pull it. And we should do it in Premier. That's a great question. In the daily adjustment of the grams per kilo of the small lipid, I still rely on the triglyceride level of patients, but does it have the same effect on the up and down of triglycerides in the daily adjustment or anything different? We don't really adjust the lipid doses too much. Our dieticians will sometimes ramp the lipids. They may start at 40 or 50 grams a day. This is for adults. And then they may ramp to 60 or 65. Now we do hypercalorically feed with TPN. I think to make TPN successful, you need to think about hyper. You don't just start at goal, right? You could, but you shouldn't. So the first few days in the ICU, we'll start at 800 calories, right? We'll start at 10, 15 per kilo, and they'll sit there for two or three days. And then they ramp up. And we start the protein at 0.8. You should ramp your protein the same way. And then our lipids typically, sometimes we're on propofol, we can't give them, but 40, 50 grams, and we hold pretty steady. We don't make many adjustments. And the triglyceride levels usually don't change very much. Some patients, if they're going to change, they just will. I think it's independent of the lipids you're giving. As you saw, we didn't see a big difference in the triglyceride levels of the patient no matter which lipid they were giving. So we did in the LFT numbers, right, the peak bilirubin, the peak AST, ALTs, those were definitely improved. But triglyceride levels, I think, is more a reflection of the patient and their physiology. And we don't change the dose very much. And you don't have to supplement anything, any extra carnitine or anything like that, levocarnitine? Sometimes. If the triglycerides are rising, we routinely supplement carnitine. For all of you who have CRT patients, which I'm guessing most of you do, that gets deficient frequently within five to seven days of being on CRT. You should be checking levels and repleting it. Copper B6. It's one of the papers we just recently published that Krista worked on with us. I didn't know that was happening until a few years ago when a burn patient taught me that. I learned it all from one big 95% burn I cared for in Metaburger's Health from Switzerland. But copper deficiency occurs in somewhere between 70% and 80% of your patients within five days. Copper deficiency is devastating, right? It leads to permanent weakness if you let it sit and don't diagnose it and treat it. B6 will uptund people. They'll look like they've had strokes and get MRIs. You give them 50 cents worth of B6 because they're level zero because the CRT is a big hole in the bottom of the bucket and it drains up micronutrients, they wake right up. And I don't know almost anyone in the world that knew that. I didn't know it. And Metaburger and I and others are really driving that home. If you have CRT patients, within five to seven days, you should be looking for your micronutrients. We need replacement. We need to come up with prophylaxis to all this. We routinely replace carnitine for those patients, though, somewhere between 300 and 600 milligrams a day if they're on CRT. Or if their triglycerides go high, our dieticians always put carnitine in. So we do use it frequently. We'll give it by itself, though, in the CRT patients. We can give it IV. If you were going to be put on, if you were going to need TPN, when would you want to be put on it? After a surgery? Within 48 hours. Thank you. And I can tell you the transplant surgeon didn't necessarily want to start it. And I compelled her to. I said, this is me. I'm the one taking on the care that I'm going to need to take on, and I want you to start it. I can't fathom how much weight I'd have lost if she'd have waited. I lost weight on TPN last time. Lots of it. Get a metabolic cart if you don't have one. That's the last thing I'm going to leave you with. You can't guess. I can't guess. My RD and my SICU, she's pretty good in the first week or two, and then it's a crapshoot. Even she's been doing it 20 years. It's amazing. We have two metabolic carts. We have three of them. We have an RD-driven service. We're happy to send you the S-bar for that if you want to get one yourself. We can also send you the S-bar for SMOF, for the lipids. We built that, too, and got that approved, so if you need that for your PNT community, we could send you the S-bar for that as well. But you need a metabolic cart, and you need your dietician to be running it. The new device is easy to run. It calibrates itself. You don't need anybody else but the dieticians or your ICU team. How often are you doing the metabolic carts? Every three plus or minus one day in the ICU, every five plus or minus one day on the floor. And we continue all the way to discharge. Yeah. Thank you. Yeah, yeah. It matters. And any time they have a major change, right? If they get septic, if they go back to the OR and have a big hit, any time they have a significant physiologic change, we tend to check again, because that's when you see changes. As a patient, I didn't change very much, interestingly. I was 3,000 before surgery. I was about 3,100 after. So some people change enormously. I've seen 2,000 calorie changes in five days. So you can't guess. Hey, thank you so much. So if I am a dietician, say, or a pharmacist at an institution that's not currently using a mixed oil formula, and I'm trying to seek input and seek support for getting that at my facility, what would be your elevator pitch? What are the things that you would be most impactful for, either physicians or administrators, to kind of convince them to bring it on? So I would say when we went in 2017, and now the data's better, we leaned on the Pradelli meta-analysis for reduced length of stay, which is where money's at, right? Length of stay is what drives cost. Reduced infections. Now we have this pre- and post-data that shows in a real... This is the first real-world U.S. practice data. We didn't say that, but I think that's one of the novel things of this study. This is the first U.S. practice data that we've had to say that there's a benefit in changing. So I think this kind of study in a real-world setting, in a real center setting where we had data, is good to drive. The cost-savings data that's been published that you saw us present the slides on, I think is helpful. In 2017, when we sold it to P&T, it was really just on the infection, the LFT changes, and on the length of stay from the original Pradelli meta-analysis, and our P&T committee thought that was more than enough for the couple-dollar-a-bag difference. That said, right now you have a lot more data you can arm yourself with. I think also the physiology, I presented at P&T myself with our pharmacists and with two of our dieticians. We presented as a group. And just when you present the physiology that you heard tonight, that was compelling for them. A lot of them said, if we didn't have the hard clinical data, we'd probably switch here and what we just heard. But we do. We have this large meta-analysis. We have cost data. We have now real-world U.S. data. Those are the three things I would lean on. Because most of the time, I think P&T will hang you up, and they'll say, oh, but it's a few dollars different. Is there really data? There is. Right? So... Especially with the infection risks, right? Because we're trying to reduce UTIs, so, I mean, if we're reducing... Yeah. I mean, there's a never-ever event right there. But... And yeah, and that was surprising to me, too. I was shocked a little bit about that being the specific thing we saw. But the length of stay data, right, is where the money's at. And we're happy to share the data and anything... These slides, we're happy to send you. So if you want to email us, and we'll send them to you to help you support your cause. So... Because I know it's a challenge. We've heard that from dieticians and pharmacists around the country, that they're still being pushed back from their P&T. I see you nodding. We want to help. From a patient's point of view, and from an academic physician's point of view, we want to help. So... Anything else? All right. Be sure you fill out your evaluations, everyone. Thank you so much. Thank you guys for coming. Thank you.

Mixed lipid emulsions

Total Parenteral Nutrition

Hospital stays

Improved outcomes

Increased fat intake

Enhanced strength

Healthcare professionals

New lipids

FDA requirements

Infection risks