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Nutrition Therapy in the ICU
721 Plays6 days ago
When it comes to critical illness, nutrition isn't just supportive care—it can be a key part of the treatment plan.
In this episode, Dr. Sergio Zanotti sits down with Dr. Jayshil Patel to discuss nutrition therapy for critically ill adults and the growing evidence behind enteral nutrition's role in improving outcomes.
Dr. Patel is a pulmonary and critical care physician in the Division of Pulmonary at the Medical College of Wisconsin whose research focuses on how enteral nutrition influences outcomes in critical care settings.
Additional resources:
- Nutrition Therapy in Critically Ill Adults. J. Patel, S McCLave. NEJM 2026.
- Trial of the Route of Early Nutritional Support in Critically Ill Adults. CALORIES Trial. NEJM 2015.
- Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). LANCET 2018.
Books mentioned in this episode:
Recommended
Transcript
Introduction to Critical Care Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine. Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com. And now your host, Dr. Sergio Zanotti.
Understanding Acute Critical Illness
00:00:32
Speaker
During the acute phase of critical illness, patients experience severe catabolism, inflammation, muscle loss, and gut dysfunction, all of which affect nutritional status and requirements.
Exploring Nutrition Therapy
00:00:43
Speaker
In today's episode of Critical Matters, we will discuss nutrition therapy for critically ill adults. Nutrition therapy, the provision of enteral or parenteral nutrition to patients enabled to maintain volition, is a fundamental aspect of critical care medicine.
00:00:58
Speaker
Yet it remains an area of uncertainty and opportunity for improvement.
Importance and Impact of Nutrition in Critical Care
00:01:02
Speaker
Our guest is Dr. Jayshil Patel, a pulmonary critical care physician in the Division of Pulmonary and Critical Care Medicine at the Medical College of Wisconsin.
00:01:11
Speaker
He's an associate professor of medicine. His research focuses on the impact of enteral nutrition on critical care outcomes. Dr. Patel has received NIH grants and has published extensively on topics related to critical care and nutrition in critically ill patients.
00:01:25
Speaker
He recently published a wonderful review article in the New England Journal of Medicine. Jay, welcome to Critical Matters. Thank you so much, Sergio, for having me. I consider it an honor to be here.
00:01:38
Speaker
We'd like to start with a general question of why should our listeners care about the topic of nutrition in critically ill patients?
00:01:48
Speaker
That's a great question. um You know, i I imagine that when most people think about the intensive care unit, and that includes our clinician colleagues, Sergio,
00:02:00
Speaker
They probably think about things like ventilators, um dialysis, ah extracorporeal membrane oxygenation or ECMO, or life-saving medications.
00:02:11
Speaker
They may not think about nutrition, but regardless of why our patients are admitted to the ICU, it turns out that nutrition touches every single one of them.
00:02:22
Speaker
In fact, their bodies undergo um an extraordinary metabolic response. They rapidly lose muscle, they develop gut dysfunction, and they become profoundly catabolic.
00:02:33
Speaker
But I'll tell you that nutrition isn't just about calories. And hopefully, as we will discuss, it's about giving the body what it needs at the right time. But I will submit to you that it's also something that matters to patients and their families.
00:02:50
Speaker
You've probably experienced this, Sergio, but one of the first questions an individual you may just have extubated might ask is, when can I eat? Families often ask, when can my loved ones receive nutrition? Are they receiving enough nutrition?
00:03:06
Speaker
And nutrition is, of course, beyond just a humane aspect of the care we provide. It also is very culturally rooted in a lot of the patients that we take care of.
00:03:17
Speaker
And so nutrition is one of the few therapies that affects every critically ill patient. And when we get it right, we're not just helping patients survive, ah we're also helping them recover.
00:03:30
Speaker
Excellent. and And it's very interesting because when when you think about and outside of the ICU, and no matter what your culture is, we've all probably experienced grandmothers who, when we were young and sick, would encourage certain types of food, right? With the idea that there are different types of food that are going to accelerate your healing, they're going to be well better tolerated. So this is something, i like you said, is deep embedded in our culture, but also in just ah human behavior. And What I also find very interesting, and we were talking about this, Jay, before we started recording, is that nutrition is one of those topics that is present in every patient that we round on every single day.
00:04:11
Speaker
Yet, I feel that there's so much that's been, that's untapped, that's not discussed, that is not really fully understood. And that's why i wanted to have you on today to to go a little bit deeper.
00:04:24
Speaker
Yeah, no, I would agree. And, you know, ah it's been it's been called a soft science in some in some circles. And um we were very intentional in in the title of this recent article. We didn't call it nutrition support for a reason, because support ah sounds passive. In fact, we call it nutrition therapy because it really is an active means and a fundamental aspect of um the care that we provide our critically ill patients. And hopefully we'll we'll discuss a little bit more about what we mean by active component.
00:04:59
Speaker
Excellent. I would like to continue our discussion with a review of pathophysiology. The acute phase of critical illness is prominent in your review article, but also in how we think about what happens to our patients in the ICU.
00:05:16
Speaker
Could you expand on that concept and how it impacts nutrition therapy?
Nutrition Therapy Strategies and Evidence
00:05:21
Speaker
Yeah, absolutely. And and I think... recognizing this biology that you're alluding to is really important to then say, what is it that nutrition can do to ameliorate um the alterations in the biology?
00:05:36
Speaker
So many of us learned, you know, the ebb and flow of critical care. But in 2019, the European Society of Parenteral and Enteral Nutrition, or ESPN,
00:05:48
Speaker
was the first to partition the phases of critical illness into the acute phase and the late phase. They further partitioned the acute phase into the early acute phase and late acute phase.
00:06:03
Speaker
Now, it turns out that one of the biggest misconceptions is that critical illness is simply the disease itself. And so whether it's things like sepsis, trauma, acute respiratory distress syndrome,
00:06:18
Speaker
But in reality, the body mounts a profound metabolic stress response during this early acute phase of critical illness.
00:06:28
Speaker
And that response is remarkably similar regardless of that initial insult. So in other words, these insults like sepsis, burns, ARDS, they unlock this metabolic response that really shifts the body into survival mode.
00:06:47
Speaker
And during this early acute phase, hormones, inflammatory mediators, ah activation of other endocrinologic responses, they drive rapid muscle breakdown.
00:07:01
Speaker
Insulin resistance develops. Hyperglycemia occurs. And one underappreciated aspect is that the gut becomes dysfunctional. So the gut barrier function is impaired. And as a consequence of this impairment in the gut barrier function, the motor ah gets turned on in the gut.
00:07:23
Speaker
And this turning on of the gut motor um leads to a perpetuation of pro-inflammatory responses that can lead to worsening organ dysfunction, downstream organ dysfunction.
00:07:36
Speaker
And what's fascinating is that this response is actually adaptive. Again, it's the body's way of trying to survive. But if this response persists, is dysfunctional, this is what contributes to that downstream organ dysfunction. But more importantly, from our patients' perspective, it contributes to that weakness, that prolonged recovery, and many of the long-term problems ICU survivors face. And so understanding this biology has really fundamentally changed how we think about nutrition therapy.
00:08:12
Speaker
And so instead of trying to outfeed the stress response, we now try to work with the body's physiology and match nutrition to the phase of illness.
00:08:27
Speaker
In terms of nutrition therapy, as we move forward and talk more about management, a I like to think about like the route, the timing, and the dose. And obviously, like like you mentioned, this impacts all our patients. There might be a subset of patients in the ICU who have volition. and that's using a surgical ICU people who are recovering that's separate but in the vast majority of our patients for whatever reason they're unable to to take their own food and at one point we have to decide okay what are we gonna do for nutrition therapy could you talk to us first about the route enteral versus parenteral and where do we stand today in terms of what the literature really supports
00:09:09
Speaker
Yeah, absolutely. um That's a wonderful question. You know, i think that one of the biggest advances in critical care nutrition over the past two decades is that we've moved beyond thinking of enteral and parenteral as competitors.
00:09:27
Speaker
And so for years, there was a perception that enteral nutrition was always the right answer and parenteral nutrition should be avoided whenever possible. But the evidence has really changed that conversation.
00:09:40
Speaker
And so indeed, if the gut is functioning and enteral nutrition can be delivered safely, it remains my preferred route because it's physiologic. It helps maintain gut integrity and it supports the microbiome.
00:09:55
Speaker
But we've also learned from large, well-conducted clinical trials that if nutrition isn't feasible or isn't safe, early short-term parenteral nutrition is a safe and appropriate alternative.
00:10:11
Speaker
So, for example, the CALORIES trial showed that early enteral and parenteral nutrition resulted in similar mortality and infectious complications. This was a large trial conducted um out of the United Kingdom.
00:10:27
Speaker
and they randomized patients to early enteral or parenteral nutrition. Now, mind you, these were also patients who didn't have contraindications to enteral nutrition, but it was a pragmatic trial.
00:10:41
Speaker
And this trial really challenged the long-held belief that parenteral nutrition was inherently more dangerous. And again, it found that there were similar outcomes related to mortality and infectious complications.
00:10:57
Speaker
The latter is important because there's still a belief that parenteral nutrition results in more infectious complications. But this trial really challenged um that ah presumption.
00:11:12
Speaker
The second trial that challenged the idea that upfront parenteral nutrition, you know, is okay, is the NUTRIA-2 trial.
00:11:24
Speaker
This was a trial that was conducted in France. It was multi-center. It was pragmatic design. And what it also demonstrated was that in mechanically ventilated patients with circulatory shock who were receiving vasopressors, enteral nutrition did not improve mortality compared with parenteral nutrition.
00:11:42
Speaker
And it was ah associated actually with more gastrointestinal complications, including bowel ischemia. And so Neutruria 2, what I took away from that is that in individuals where you might be hesitant to start enteral nutrition because of, say, the risk of bowel ischemia is high, or, for example, there's just a mechanical obstruction, then early parenteral nutrition is a safe i'll alternative. it six So today, i don't think the question is which route is better. i think the question is what's the right route for this patient today?
00:12:20
Speaker
And so we shouldn't force enteral nutrition at all costs. And we shouldn't hesitate to use parenteral nutrition when it's indicated. i think good critical care is about individualizing therapy um rather than just following dogma. So all in all, I think we have evidence from large multi-center randomized control trials that tell us that parenteral nutrition is a safe alternative when enteral is contraindicated or the clinician is just hesitant to use it.
00:12:52
Speaker
And it's important because like you mentioned, the the choice of the appropriate nutritional therapy is no different than so many other choices. And yet, because of guidelines, because of how we're being educated, it becomes a dichotomy for a lot of people, this or that. And the the the real idea, like you mentioned, is to be thoughtful as critical care experts of what's the best therapy for the patient in front of me.
00:13:20
Speaker
and And that really should be should be the emphasis. but But I remember, I mean, I've been in practice long enough, Jay, that I remember how much parenteral nutrition we would prescribe in the ICU, right?
00:13:33
Speaker
How that eventually dwindled down. And it's almost like the pendulum now is going again the other way. You're almost like you use no parent parental nutrition. all of a sudden, okay, there might be some patients in whom that's the right answer.
00:13:46
Speaker
So really trying to to find that that balance is very important. Yeah, absolutely. One thing I say is you know, feed the patient, not your bias, right? And so again, yeah.
00:13:59
Speaker
And so if the gut is functioning and it can be done safely, enteral is still my first choice for sure. um But, you know, people are rightfully responsible. concerned about bowel ischemia, uncontrolled shock, or some other contraindication, then of course withholding enteral attrition is reasonable. um But if you're reluctant to use parenteral attrition, well, that also isn't helping our patients.
00:14:25
Speaker
I want to talk about timing. And you mentioned early. Could you be more specific? How early? How do you think about early versus late in terms of nutrition therapy support?
00:14:38
Speaker
Yeah, absolutely. You know, let me preface by saying that I think that one of the biggest shifts in our thinking is that early does not necessarily mean full dose. And I know we'll get to dose in a little bit.
00:14:52
Speaker
But for most critically ill patients, if the GI tract is functional, again, and there's no contraindications, I would consider starting enteral nutrition within the first 24 to 36 hours. And I'm just following what the evidence tells us. So for example, the evidence supporting this approach comes from a meta-analysis of over 20 randomized controlled trials.
00:15:17
Speaker
showing that early enteral nutrition started in that window of 24 to 36 hours was associated with better outcomes. And these outcomes include mortality as well as infectious complications. And this was compared to delayed feeding or no enteral nutrition.
00:15:36
Speaker
And the likely benefit is not simply the calories, but it may help preserve gut integrity. Again, support the intestinal microbiome and maintain immune function.
00:15:48
Speaker
But starting early is different than trying to reach full caloric targets immediately. Again, during that early acute phase of critical illness, patients are highly inflamed, they're catabolic, and they're relatively resistant to using nutrients for rebuilding ah muscle.
00:16:07
Speaker
So my approach is to start early, and I know we'll get to this, but the punchline here is that you start at a lower dose and advance thoughtfully. And so the practical message is start nutrition early when it is safe, but do not rush to full feeding.
00:16:25
Speaker
Excellent. The other aspect that you mentioned a regarding and the route, it was bowel ischemia. And one of the most common discussions that we have during rounds is, are we okay to start enteral nutrition in a patient on vasopressors?
00:16:44
Speaker
And I know that this is something that has not been addressed specifically with a dedicated randomized trial, but there is data from other trials that might guide our thought in this in this area. Could you expand on um that issue?
00:16:58
Speaker
Yeah, absolutely. um This topic is music to my ears. um This was one of the reasons I decided to um study the role of nutrition therapy in critical care outcomes. You know, if I may, um when I was a fellow, I remember, and you might as well, that You know, we had, again, this sort of two attending phenomena. One attending might say, hey, start nutrition in this patient in shock. And the other attending might say, well, what are you doing? why Why do you want to start nutrition in this patient in shock? We should wait till they're out of shock.
00:17:31
Speaker
And when we sort of push a little bit and say, well, you know why are you saying what you're saying? a lot of it is just based on anecdotal evidence, or at least at the time it was based on anecdotal evidence. You are absolutely right. We just don't have large scale randomized controlled trials that tell us what to how to how to feed people in terms of timing who are on vasopressors.
00:17:54
Speaker
Now, what I will say is that vasopressor use by itself is not an absolute contraindication to initiating enteral nutrition. And the key questions are whether the patient is adequately resuscitated, whether the vasopressor dose is stable or decreasing, and whether there are other signs of gastrointestinal hyperperfusion or intolerance.
00:18:16
Speaker
And you know this, Sergio, um but in individuals who are on vasopressors, there's reduced gut splenic blood flow.
00:18:29
Speaker
And so when we introduce something enterally, there's a risk of having diminished ATP at the level of the gut for the gut to actually do its job and process and digest um those delivered nutrients. And so there's a mismatch between the amount of oxygen available and the amount of available.
00:18:51
Speaker
that is really needed to carry out the gut's functions. And that creates an environment then for ischemia, which is the most grave consequence.
00:19:03
Speaker
But what does the literature tell us? Well, I think the literature tells us to be cautious with early full dose feeding in severe shock.
Risks in Nutrition Therapy
00:19:11
Speaker
And so this comes from the Neutria 2 trial. So if you recall, Neutria 2 randomized mechanically ventilated adults who were in circulatory shock. About two-thirds of them had septic shock to receive early full-dose enteral nutrition or early full-dose parenteral nutrition.
00:19:34
Speaker
And again, the punchline from that trial is that there was no difference between group difference in mortality. um And again, it told us that early parenteral nutrition is a safe um alternative.
00:19:48
Speaker
But in the group that received early full-dose enteral nutrition, there were a lot more gastrointestinal complications, including a significant difference in bowel ischemia.
00:20:01
Speaker
And so Neutruria-2 really was the first trial that told us that, hey, we should pump the brakes in terms of the quantity of nutrition that we deliver, enteral nutrition we deliver to our critically ill patients who are in circulatory shock. And one of the underappreciated aspects about the Neutruria-2 trial is that in the patients who received early full-dose enteral nutrition,
00:20:30
Speaker
they were receiving 0.5 mics per kg per minute of norepinephrine equivalent. Now, I don't know what that's like um where you practice or where you used to practice, but at some institutions, um that is considered a high dose.
00:20:49
Speaker
What do you think? Is that a high dose for use of practice? And I think that what I encounter more often in practice is somebody is on vasopressors, naturally a high dose.
00:21:01
Speaker
Their MAP is controlled, right? And people say, do we do we not, right? but But I do think that there's also, recitation, my experience is that... there's refractory shock or early shock when you're trying to get there and you're going at higher doses, but that's usually not the place where I would be thinking of nutrition, right?
00:21:21
Speaker
That's a lot very acute. So I think it's a, it's a, it's a, it's a real dose, right? Yeah. yeah And I think many of our colleagues would agree with that, that that is a pretty high dose and you know, it's, o um you know,
00:21:38
Speaker
of pouring gasoline onto a spark. Right. And so, and so that was one of the things that we learned from Neutria 2. And it turns out that Neutria 3 reinforced that concern. So Neutria 3 took the same patient population, mechanically ventilated adults with circulatory shock. Again, two thirds of them had septic shock.
00:22:02
Speaker
And they were on 0.5 mics per kg per minute. And what they did in that trial was they randomized individuals to a lower dose of nutrition. So six kilocal per kg versus full dose enteral nutrition. And it reinforced that concern by showing, again, more adverse events with full dose nutrition than restrictive dose in patients with circulatory shock. But again, importantly, many of these patients were receiving norepinephrine at that high dose of 0.5 mics per kg per minute. So what does what does ah the rest of the literature tell us? Well, it turns out that
00:22:40
Speaker
at lower or moderate basal presser doses, there's emerging evidence to suggest that low dose or trophic internal attrition may be safe, particularly when the patient is hemodynamically improving. But here's the here's the kicker. We still do not have a universally accepted basal presser dose cut off.
00:22:59
Speaker
and And we know this from survey data that um our group has done. So if you ask two clinicians, for example, hey, what does a low dose norepinephrine look like? You know, some might say under 0.1 mics per kg per minute. Somebody else might say under 0.2 mics per kg per minute. And so I think there's still be work to done to sort of unify and and figure out what low, moderate doses of of vasopressors mean. So my practical approach is i don't feed in an escalating shock state and once once resuscitation is adequate and the vasopressor requirement is stable, um I will start a restrictive dose, trophic dose, enteral nutrition and I advance you know cautiously. And we'll get to it a little bit in terms of the dose itself and and the rationale for the dose. But that is my approach in terms of feeding patients on vasopressors. And I will say that looking ahead, i think this is one of the biggest gaps in our knowledge is defining the optimal timing of nutrition in patients with circulatory shock, particularly because...
00:24:09
Speaker
not just because it's, it's of course, um my area of interest or my bias, but I think it's because these are the patients that a little bit of nutrition into the gut stands to have the greatest benefit. These are sick individuals, and so protecting their gut, they may stand to derive the greatest benefit. But again, we need well-designed clinical trials comparing different timing strategies across the the spectrum of shock, not just septic shock.
00:24:37
Speaker
Yeah, and it's a very relevant topic as well because my my my gut instinct is that we're going to see more and more people started on vasopressors earlier and get less fluid based on ARISE and many other studies, right? We also now can can give vasopressors in many places without a central line, initiate them. So again, I mean, trying to distinguish who requires some vasopressor support versus who has refractory shock or escalating doses of ah vasopressors are two different groups. And I think that the first group is more common.
00:25:16
Speaker
And like you said, I mean, providing benefit of... starting nutrition without necessarily yet at a full dose, like we'll talk, and my might outweigh the risk and might be the way to go. So more more to come, but your practical advice is very well taken. And I would encourage our listeners to ah think about this and talk more about it during rounds.
00:25:38
Speaker
Let's talk about dosing, if it's okay. And I know that there's different strategies and that we can we can get to that. But just what I would love to to hear from you, Jay, is how do we think about proper dosing? And I remember taking boards for the first time 20 plus, 25 years ago And I remember very, very vividly that one of the questions would be the dose of parenteral nutrition in a critically ill patient. And they want you to calculate calories, how much protein.
00:26:12
Speaker
And my sense is that the answer back then that was right is probably not the right answer today. So if you could just ah expand on that. Yeah, absolutely. And and this is a a wonderful subtopic and one of my
Nutrition Responsiveness and Patient Outcomes
00:26:28
Speaker
favorites, actually. And, you know, i think this is also be one of the biggest shifts in our thinking is that the question isn't simply just how many calories should we give.
00:26:39
Speaker
So let me take a step back and and um please pardon me if I get a little too excited here. But um going back to that early acute phase of critical illness, Remember, patients are inflamed, they have insulin resistance, they have anabolic resistance, they mitochondrial um dysfunction, and the mitochondria are the are the batteries, you know, that um help us ah fuel the cell to to do its job, including the cells in the gut to do their job, you know, as well.
00:27:13
Speaker
And so what's happening during this early acute phase, it turns out that the biologic capacity to utilize nutrients is really limited. And so intuitively we might say, if this individual is developing a caloric debt, intuitively, why don't we just give them back as many calories as possible during this early acute phase? Let's try and close this caloric debt as much as possible.
00:27:45
Speaker
But it turns out that giving more calories doesn't necessarily translate into greater benefit. And it may actually increase the risk of complications.
00:27:57
Speaker
And so one concept that we've recently described is this idea of nutrition responsiveness. So Sergio, um you know, doing what you've been doing for for as long as you have, I'm sure this term has come up plenty.
00:28:15
Speaker
So you've heard of things like peep responsiveness. You've heard of things like um fluid responsiveness, antibiotic responsiveness.
00:28:26
Speaker
But in the critical care nutrition world, we don't use that word. We don't use nutrition responsiveness. We just sort of presume that whatever I deliver is going to be digested.
00:28:40
Speaker
um It's going to be absorbed. And then it's going to be assimilated. and it turns out that that's just not the case. And major nutrition trials sort of support this concept.
00:28:56
Speaker
And so, for example, studies such as EDEN, Hermit, Target, the recently mentioned Nutria-3, All of these trials compared some form of restrictive nutrition dose, so a little bit of nutrition, to full dose nutrition. And I'll and i'll define these. um Full dose is generally achieving 70% to 100% of a prescribed energy.
00:29:28
Speaker
When we think about restrictive dose nutrition, Many of of your listeners may have heard of terms such as trophic dose. Well, the word trophic just means nourishment or growth.
00:29:40
Speaker
And in general, it refers to 10 to 20 mLs per hour delivery of an isoosmotic formula.
00:29:52
Speaker
Your listeners may have also heard the term hypocaloric. Hypocaloric just means you deliver 40 70% of
00:30:01
Speaker
but you preserve the protein dose at more than 1.2 grams. And your listeners um may have also said ah for the dose ah excuse me heard heard of a restrictive form where it's just under 70%, meaning all of the calories that come from ah glucose as well as protein is under 70%.
00:30:25
Speaker
But I'm just going to use the word restrictive to define those. And the reason why is because these trials used variations in each of these. The point being that these trials consisted that delivering full calories early in critical illness, that first week of critical illness, didn't improve major outcomes and they often increased gastrointestinal or metabolic complications.
00:30:49
Speaker
And so these studies suggest that more nutrition early isn't necessarily better. It may simply exceed the patient's ability to benefit from it.
00:31:00
Speaker
And so if we go back to this term nutrition responsiveness that really forces us to ask the question, what does responsiveness mean?
00:31:11
Speaker
And what I'll submit to you is that nutrition responsiveness depends on the phase of illness. So what is it that we want our nutrition to do during which phase of critical illness.
00:31:26
Speaker
So if we're talking about that early acute phase of critical illness, which is arbitrarily the first few days, maybe up to the first week of critical illness, then I want enterally delivered nutrition to support the gut architecture and to support the gut functions.
00:31:46
Speaker
And the reason I want that is because i recognize that when the gut is dysfunctional, that it leads to worse outcomes. So notice, I'm not saying i want nutrition early close my calorie debt, to provide an anabolic response to produce protein in the muscle.
00:32:11
Speaker
And the reason is, is because I recognize that nutrition in that early acute phase has limited capacity to actually do that. And it's offset by the complications that are observed in these landmark randomized control trials. And again, these complications include things like vomiting, development of enteral feeding intolerance, development of worsening hyperglycemia, and in some studies, surrogates of mitochondrial dysfunction, which include worsening lactic acidosis, inability to get off the ventilator faster.
00:32:48
Speaker
And so I want to caution the audience and really, um really drive this point home that I think the pendulum is shifting towards a less is more strategy during this early acute phase of critical illness, whereby that term responsiveness really means support the gut architecture and, um, its functions. Now, if we move into the later phases of critical illness, so for example, um,
00:33:20
Speaker
your patients defervesce, the FiO2 and PEEP requirements are coming down, the vasopressor doses are coming down or off, your patients are now awake, they're alert. Well, now we're transitioning. Now we're moving towards a new phase. And um there may be more of an anabolic response.
00:33:40
Speaker
There may be greater capacity to handle the calories that are given to your patients. And so as we move away from that early acute phase of critical illness, well, this might be the time where responsiveness means something different. And responsiveness in this phase means I'm not only going to digest, but I'm going to absorb.
00:34:05
Speaker
And I'm going to assimilate. so I'm going to utilize the calories. I'm not just going to oxidize and create more ah metabolic stress, but I'm going to utilize the calories. I'm going to utilize the protein. And so really important concept. And I think a concept that we should start using in our rounds, nutrition responsiveness.
00:34:28
Speaker
Absolutely. And like any other therapy, right? We implement the therapy and we evaluate how are they responding to that?
00:34:39
Speaker
Yeah, absolutely. Yep, absolutely. In terms of, a so you talked about proper dosing, how to think about it today. We talked about different strategies with a restrictive that includes trophic, hypocaloric, permissive maybe, and full dose.
00:34:56
Speaker
What about protein? How has our thought about protein evolved over the years based on the studies? Yeah, that is another topic that's sort of near near and dear to me. um I think protein is especially important because as we've already mentioned, um critical illness causes sort of rapid and and profound muscle breakdown. One thing I i teach consistently is, Sergio, if if you were to stop eating today, right, and and and you're a relatively healthy individual, then the order of substrate utilization for you would be glycogen, fats,
00:35:38
Speaker
that's as a source of ketones for energy, and then protein. Now, in our critically ill patients, the latter two are reversed.
00:35:50
Speaker
So for them, it's glucose, in fact, gluconeogenesis, proteolysis, and then fatty acid oxidation.
00:36:02
Speaker
And Most of the proteolysis that occurs comes from the muscle. And so inflammation, stress hormones, immobility, insulin resistance, all of these activate proteolytic pathways. And there's a common pathway called the ubiquitin proteosome ah system, which essentially tags muscle proteins for degradation.
00:36:27
Speaker
And so those amino acids are then redirected towards gluconeogenesis, immune function, wound healing, and the production of acute phase proteins.
00:36:38
Speaker
And you know what? The magnitude of the loss is striking. So we have data that tells us that critically adults lose approximately 2% of their skeletal muscle per day during the first week in the ICU.
00:36:52
Speaker
And that's roughly 10 to 15% within week. within a week And then that proteolysis can conter can continue into the second week. And in survivors of trauma, that can continue even after discharge.
00:37:07
Speaker
And so this partly explains the severe weakness and prolonged functional impairments that we see among ICU survivors. So if I stop right there, if your listeners just hear that part of the story, intuitively, they might say,
00:37:25
Speaker
wow, we should be giving protein. We should be giving as much protein as we can to our critically ill patients. That biology, in fact, led us to assume that giving substantially more protein would preserve muscle. And we have tons of observational data that seem to suggest that more is better.
00:37:47
Speaker
We even had some observational data that suggested that less actually was better. But overall, the problem is anabolic resistance.
00:37:58
Speaker
And so patients absorb amino acids normally, but yet they incorporate far fewer of them into new muscle protein. There's some sophisticated amino acid tracer data that came out of a group in Australia. And what they found was that compared to you know healthy controls,
00:38:19
Speaker
critically ill adults just didn't assimilate the protein, the amino acids that were delivered compared to healthy adults. That physiologic study found that they incorporated only about 60% as much as of the amino acids as the healthy the adults.
00:38:37
Speaker
In other words, the substrate gets into the circulation, but the muscle just cannot use it efficiently. And so for many In many ways, there was equipoise around the question of how much protein to deliver.
00:38:51
Speaker
So back in 2016, the American Society of Parenteral and Internal Nutrition and the Society of Critical Care Medicine guidelines um recommended giving at least 1.2 grams per kilo per day and more in other ah subpopulations.
00:39:08
Speaker
And we didn't have large scale randomized control trials that um told us anything different. But you know what? Major randomized trials since then have been quite sobering.
00:39:21
Speaker
The first one was called the effort protein trial.
Protein Intake Findings in Critical Care
00:39:24
Speaker
And the effort protein trial compared 1.2 versus 2.2, at least 2.2 grams per kilogram per day.
00:39:33
Speaker
And it turns out that it found no improvement in time to discharge alive, which was the primary outcome. But it also found signals of harm. in patients with greater severity of illness and those with acute kidney injury not receiving dialysis. Meaning um chances of getting out of the hospital alive were reduced, increased risk of mortality, associated mortality in those individuals who had a higher severity of illness score, the SOPA score, and those who had acute kidney injury.
00:40:08
Speaker
The second randomized control trial that's been done is called the PRECISE trial. They also randomized critically ill adults to higher or lower protein doses. And they actually found more feeding-related adverse events and worse, longer-term quality of life outcomes at 2 grams per day versus those who had 1.3 grams per kilogram per day.
00:40:33
Speaker
And the third trial that was quite sobering was called the TARGET protein trial. It also compared a higher to lower protein dose, and it found no improvement in days alive and out of the hospital with augmented protein delivery.
00:40:52
Speaker
And so even though our intuition tells us, hey, more protein is probably better because here's what happens to our patients over the course of their critical illness. We now have three major, what I call landmark randomized controlled trials comparing higher to low lower or protein doses that found um no benefit of higher protein. And some have found worse outcomes in subgroups.
00:41:20
Speaker
who received higher protein. And so what I want to emphasize is that the lesson is not that protein is unimportant.
00:41:30
Speaker
It's that we probably cannot overcome that acute phase anabolic resistance simply by giving more protein. And so my approach is to avoid Very high protein doses early, especially in patients with severe organ failure or acute kidney injury.
00:41:49
Speaker
And again, as we move away from that early acute phase of critical illness, it's sort of to do a increase the protein dose thoughtfully.
00:42:00
Speaker
And as the patient stabilizes, um increase it to levels where um they may actually assimilate the amino acids into what we want, which is to build new muscle, which is ultimately sort of the driver of our physical function.
00:42:21
Speaker
And so early muscle loss is not simply a protein deficiency problem. It's also a problem of accelerated breakdown and, of course, impaired protein utilization.
00:42:33
Speaker
And as many other examples in critical care, when we think that there's a deficiency, just replacing it immediately is not always the solution. That's why we need these clinical trials to really tell us what's the impact um on patient outcomes. so that's very helpful.
00:42:50
Speaker
you Yeah. And, you know, what a one other point I would emphasize, Sergio, is, you know, patients who are malnourished, um we often think, hey, when somebody comes in malnourished, I just want to feed them.
00:43:03
Speaker
You know, i want to give them protein. I want to try and get as much into them as we can. And, you know. high and low doses of protein, there have been secondary analyses of the effort trial, effort protein trial, that have also showed that um more protein doesn't modify the association between malnourishment and improved outcomes. And so even in that population, there's still, of course, a lot to be learned, but the available evidence that we have right now doesn't seem to suggest a signal for higher protein.
00:43:35
Speaker
Excellent. You talked about nutrition responsiveness. So that implies that we have to monitor our patients who are being treated with nutrition therapy.
00:43:47
Speaker
and My first question in this, in this area is, can we stop checking gastric residuals? Yeah, that's a, that's a great question. um I think, I think one of the, that's one of the biggest changes in our field is recognizing that, um,
00:44:08
Speaker
recognizing that not all gastrointestinal findings carry the same significance. And before I answer that question directly, i do want to talk a little bit about um the difference between the types of gastrointestinal findings. And so we outline what are called low risk findings.
00:44:26
Speaker
And low risk findings are things such as gastric distention, ileus, a little bit of nausea, even vomiting, um and elevated gastric residual volumes.
00:44:37
Speaker
What's really important is that these low-risk findings should be taken in the context of what's happening with the patient and shouldn't automatically prompt us to stop enteral nutrition.
00:44:49
Speaker
In fact, um the evidence over the past decade has shown us that gastric residual volume is a poor predictor of things like aspiration or pneumonia.
00:44:59
Speaker
And there's landmark trials. One of them is by Rainier and colleagues. So earlier I talked about the Neutruria-2 and the Neutruria-3 trials. Well, it turns out that the Neutruria-1 trial tested gastric residual all you monitoring or not in critically ill adults. And what they found was that eliminating routine gastric residual volume monitoring did not increase ventilator-associated pneumonia. It did not increase ICU-acquired infections or mortality.
00:45:32
Speaker
But what it did allow was for patients to receive more enteral nutrition. And similarly, um the REGAIN trial found similar findings. So today i don't routinely stop enteral nutrition because of an isolated elevated gastric residual volume. And in fact, I'll take it one step further and say we probably should stop measuring gastric residual volume. It's one of the things that my nursing colleagues still continue to do. It's still one of the things that's taught, of course, nutrition.
00:46:04
Speaker
ah throughout nursing school, but I think it's just ah ah something that we have to do a better job of in terms of disseminating the results of these large trials that tell us that we can probably stop ah measuring gastric residual volumes. Now, earlier i talked about the low risk findings, but what concerns me more are high risk findings.
00:46:27
Speaker
And so these high risk findings include things like worsening abdominal pain, worsening distension, rising lactic acid, signs of mesoteric ischemia, bowel necrosis, and of course, abdominal compartment syndrome. And I think the important point is that the same finding can have a very different meaning depending on the patients. So for example,
00:46:51
Speaker
Mild gastric distension in a stable patient may simply warrant observation. And so that stable patient might be somebody who is, for example, not receiving vasopressors.
00:47:02
Speaker
Whereas similar findings in a patient with worsening septic shock receiving vasopressors may actually represent evolving ball ischemia. So I think rather than asking, does this patient have eating intolerance? um I now ask, is this a low risk finding that I can manage while continuing nutrition? Or is this an early warning sign of something a little bit more serious?
00:47:27
Speaker
And I think that requires a much more individualized approach and one that helps us avoid unnecessary interruptions, for example, by measuring gastric residual volumes.
00:47:37
Speaker
um and delayed recognition of life-threatening gastrointestinal complications. Another complication that I've encountered more often in and books and in questions, but still remains very important to recognize and especially to avoid is refeeding syndrome.
00:47:57
Speaker
Could you mention and some tips on refeeding syndrome? Yeah, absolutely. um You know, I think it may be under-recognized, and I think it may continue to be under-recognized, and here's why. um i think it's important for us to identify malnutrition in our critically ill adults. So it's remarkably common in the ICU, and contemporary data tell us that, you know, more than 40% of critical adults are already malnourished malnourished even before they arrive to the icu
00:48:34
Speaker
And they often, um many of our other individuals who aren't necessarily malnourished before they arrive to the ICU will have other risk factors for repeating syndrome. So for example, they might have lost um a few pounds before coming to the hospital. They might have had poor oral intake as a result of their illness that was developing before they became critically ill.
00:48:57
Speaker
And We certainly want to recognize these individuals, not necessarily because we want to so supplement them with more calories, because remember, we're moving towards a less is more approach.
00:49:11
Speaker
We want to recognize these and individuals because of their risk for refeeding syndrome. And ah as you know, the hallmark of refeeding is hypophosphatemia.
Addressing Refeeding Syndrome and Hyperglycemia
00:49:23
Speaker
And so The reason to recognize this risk is because we want to be careful of how quickly we advance nutrition in these individuals. And sometimes it's not even um what we intentionally deliver enterally or parenterally. It might even be the dextrose that is in the antibiotic. It might even be the dextrose that is in some other IV formulation that we're using for these individuals.
00:49:52
Speaker
And the hallmark is ah reduction in the phosphate after we provide a little bit of sugar to these individuals. And we often see not just the hypophosphatemia, but what may follow is hypomagnesemia, hypokalemia.
00:50:10
Speaker
Some of these individuals might be quite deficient thiamine as well. And so it can lead to deleterious consequences such as arrhythmias, cardiomyopathy, muscle weakness, for example.
00:50:24
Speaker
And one of the trials that informed this was done by DOIG. It was called the refeeding trial. And what they did was they wanted to see um what would happen to individual patients who were randomized to a slow ramp up in nutrition that was informed by the serum phosphate levels being reduced.
00:50:46
Speaker
or starting full dose enteral nutrition in individuals. And so they took individuals who had hypophosphatemia. So those individuals who had ah signs of refeeding syndrome, risk factors for refeeding syndrome.
00:51:01
Speaker
And what they found was that um in the group that got full dose nutrition upfront, like achieved within the first 24 to 48 hours versus the slow steady increase while monitoring and replacing um phosphate levels, they had much worse outcomes at six months. If you look at the Kaplan-Meier curve in that study, there was a wide separation in that Kaplan-Meier curve in terms of six-month mortality. It's one of the underappreciated aspects of that trial.
00:51:29
Speaker
And so um in my practice, if I recognize that somebody is malnourished before they come to the ICU and our, and our dietician colleagues do a great job of helping us recognize those individuals, or if individuals just have other risk factors for refeeding, it's very informative in terms of making me monitor their FOS, being really diligent and looking at their FOS levels a couple of times a day which then helps inform how quickly, um
00:52:00
Speaker
or not, I increase their their nutrition ah delivery. But then it also helps me say, you know what, I should give this person high-dose time and hey, I should really monitor their potassium, their magnesium at the same frequency that I monitor their phosphate levels. And so I think it's an ah overall under-recognized phenomenon, and not but something that will be really important as we move forward, as we take care of aging populations, as we do as we have more malnourished patients enter our ICUs.
00:52:33
Speaker
Excellent. Any comments, Jay, hyperglycemia? evening You know, I think there is um sort of an endogenous glucose production that occurs in individuals during that early acute phase of critical illness. So, for example, think We talked earlier about the shuffling of amino acids into the liver during the acute phase of critical illness. Well, um the fate of that circulating alanine, for example, is for gluconeogenesis. And so there is an endogenous production of glucose that contributes to the hyperglycemia that we see in many of our critically ill adults. That is just um that that is also in addition to the um anabolic production the insulin resistance that we see as well.
00:53:24
Speaker
And so giving those individuals more nutrition, what we've seen from landmark randomized controlled trials is that it, of course, worsens the hyperglycemia, but those patients also require greater doses of insulin. And so I do think that keeping the um glucose of under 180, which is what the recent SCCM ah guideline ah recommends is appropriate. And one way to do that is to not flood the body with um ah large doses of enteral nutrition when they're in that early acute phase of critical illness.
00:54:03
Speaker
We covered a lot of a lot of ground and a lot of very important topics. As we start summarizing it and closing, could you provide a clinical pearls and pitfalls for nutrition therapy in the ICU?
Best Practices in ICU Nutrition Management
00:54:16
Speaker
And maybe we can start with the top three pearls from Jay to our audience to consider.
00:54:22
Speaker
Yeah, thank you. um You know, i think the first thing I'll say is that nutrition therapy should match ah the phase of critical illness. And so we need to, I think, employ um additional language. And so we should start talking about nutrition responsiveness. And so what does nutrition responsiveness mean during the acute phase of critical illness? And what does it mean during the later phases of critical illness? And as teams start to have this conversation, they might pick up on
00:54:56
Speaker
preserving the gut architecture during the acute phase of critical illness. And i recognize then that um a little bit that goes a long ways as well. So again, nutrition therapy should match the phase of critical illness, maybe start to incorporate responsiveness as the way we do with other forms of therapies in the ICU.
00:55:14
Speaker
The second pearl is, and this is maybe just an extension of the first, that more isn't necessarily better. And that includes both total energy and protein. And I think we're moving towards a less is more strategy. We've moved towards a less is more strategy. And remember that our goals aren't to close calorie deficiencies, build muscle during that acute phase. Our goals are simply just to preserve gut architecture without causing undue harm in the form of enteral feeding intolerance, mitochondrial dysfunction, um impairments in autophagy.
00:55:56
Speaker
forcing hyperglycemia. So again, a less is more strategy goes a long way during that early acute phase of critical illness. And then the third pearl, um which I'll touch on is I think the future is individualized nutrition.
00:56:10
Speaker
um This is a really important concept as well, because, you know, no two critically ill patients are alike. There's tremendous heterogeneity. um And so then it stands to reason that um no two patients are going to respond to our nutrition prescriptions during critical illness. And so right now, you know, we talked about less is more towards sort of a heterogeneous population of critically adults. But it turns out that there may be individuals who do benefit from full dose. nutrition ah during the acute phase of critical illness. There may be some individuals who benefit from no nutrition during the early acute phase of critical illness. And so it's upon us to really identify who these individuals are. And so that requires us to look at things such as biomarkers, look at um the use of artificial intelligence in helping us really sort through um things that we just cannot see, but the machines can see. and figure out who will truly benefit from our um nutrition prescriptions.
00:57:15
Speaker
Jay, could you share the top two pitfalls to avoid?
00:57:21
Speaker
Yeah, and i and I think they're related to the top three pearls. um The first thing I'll say is don't try and outfeed the stress response. you know Many of your critically ill patients, again, will be inflamed, will be catabolic, they'll have proteolysis. um Don't try and outfeed those responses because doing so with evidence from large randomized controlled trials have shown us that um it's you may cause harm in some patients.
00:57:52
Speaker
And then the second pitfall is don't confuse feeding intolerance with gastrointestinal failure. So for example, when a patient develops um vomiting, it might be because the pylorus is closed, motility is slowed.
00:58:12
Speaker
But that tells us nothing about other downstream gastrointestinal functions. So, for example, that tells us nothing about the ability to digest, about the ability to absorb.
00:58:25
Speaker
and so that patient might need something just to push that nutrition into the space that does the digesting and absorbing. And so a motility issue does not imply, for example, pure gastrointestinal failure.
00:58:42
Speaker
Perfect. Jay, we'd like to close the podcast with a couple of questions that are unrelated to the clinical topic. Would that be okay?
00:58:53
Speaker
Absolutely. The first question relates to books. Is there a book that you read a recently or before that had a real impact on you?
00:59:05
Speaker
Yeah, that's a great question. um You know, I read... um The Road to Character ah David Brooks.
00:59:16
Speaker
This book was released, I believe, in two thousand fifteen sixteen It was around the time when um you know our first child was turning ah four or five years old. So we had you know young children and having young children certainly makes us think about a lot of things.
00:59:33
Speaker
And I recently had a chance to reread parts of it. um But The Road to Character, um it tells stories of historical figures. And it tells stories of their lives and it illustrates the development of what David Brooks calls um eulogy virtues. And eulogy virtues are like inner qualities. They're things related to our character, humility, courage, for example, moral depth, for example.
00:59:58
Speaker
And he contrasts that to what many of us strive for um in Western society. which is called Resume Virtues, which is a focus on achievement and success.
01:00:12
Speaker
And i think Brooke argues that the qualities like humility, kindness, integrity, ultimately define who we are more than our achievements. And I think that's a valuable perspective in medicine, where it's easy to focus on accomplishments, but just as important to remember the kind of position and really the kind of person that you want to become.
01:00:32
Speaker
So the road to character is something that makes me think. often Perfect. And I think that the idea of eulogy traits really are, at the end of the day, the only thing that matters is what do the people closest to us think about when we die, right?
01:00:48
Speaker
and And the idea of what would you want people to remember or say at your funeral, which is a bit morbid, but I think it's a great way of thinking it, right? And and the truth is, nobody's going to talk about our eulogy.
01:01:00
Speaker
grants or our publications or our titles, right? They're going to talk about those character traits that ultimately have the greatest impact on the life of other people. So that that's a great recommendation and definitely we'll we'll we'll link it in the show notes.
01:01:16
Speaker
The second question it relates to changing our minds. Could you tell us, Jay, something you have changed your mind about in the last few years?
01:01:26
Speaker
Yeah, that's another question. really insightful um question. um this is This is something that's an evolution for me, um but I've become much more comfortable with discomfort and uncertainty.
01:01:48
Speaker
And I read about this um as well, but you know early in my career, I really wanted medicine to have clear maybe definitive answers And I think what I've realized is that many of the most important questions don't have simple answers.
01:02:06
Speaker
And i think our job isn't to ah eliminate uncertainty. i think it's to make thoughtful decisions using the best available evidence. And it's also important to recognize then that our thoughts and our views and our beliefs have to change over time.
01:02:26
Speaker
which means that I think we have to be comfortable in uncertainty. So I'm learning to become more uncomfortable um in uncertainty. and And I think that's made me a better clinician. and I think patients and their families appreciate it when we simply just say things like, we don't know, but here's what, you know, the physiology might tell us, or here's what the available observational evidence might tell us. And it's something that keeps us, um,
01:02:55
Speaker
moving forward. And I think that curiosity that we retain from living in uncertainty might actually be the antidote for burnout.
01:03:08
Speaker
That's a great, a great and area to to talk about. And outside of the bedside, a very famous and a poet, John Keats, talked many years ago about negative capability, which is the ability to grapple with uncertainty.
01:03:24
Speaker
And the just accept it. Right. And I do believe that at the bedside, but also in everything that has to do with life outside of the bedside, that is a skill that we need to or a muscle we need to to develop.
01:03:38
Speaker
Because I do agree, it helps us tremendously with with framing the world and our profession and probably is one of the main antidotes to to burnout. I really like that.
01:03:53
Speaker
So to finish, thank you to finish Jay, could you, what would you want every listener to
Holistic Patient Nourishment
01:03:58
Speaker
know? It could be a quote or a final thought.
01:04:02
Speaker
Oh man, how much time do you have? um you know, i learned a long time ago that, um, you know, it's important to treat the disease, but we shouldn't forget to nourish our patients.
01:04:16
Speaker
And, One is intended there, and I'll explain why But I think the greatest advances in medicine aren't always like new drugs or new technology.
01:04:29
Speaker
You know, I remember being um o fellow, and I remember having this hubris whereby when my critically ill patient who just spent three weeks in an ICU finally leaves the ICU, you would i would watch them in the gurney,
01:04:48
Speaker
leave the ICU and the only part of them that would be really moving was their hands because they'd be waving goodbye to us.
01:04:59
Speaker
And the hubris in me said, we just saved a life. But what I didn't realize is that that patient needed a lot of nourishment while they were in the ICU and not just in the form of nutrition.
01:05:13
Speaker
but they will probably need a ton more nourishment once they leave the ICU because I had no clue what was going to happen to that person once they left the ICU. And it took me, of course, more training, more reading to learn what that patient truly was going to encounter once they left um our hands.
01:05:38
Speaker
But I think that... um The simple things that we do well, better more than some of the fancy drugs, fancy technologies.
01:05:50
Speaker
And so it's things like taking time to examine our patients, sitting at eye level to explain what's happening, you know, reassure families that they're safe.
01:06:01
Speaker
Oftentimes I found that patients wake up in a panic and it just requires us to say, Hey, you're safe. You're in a very safe place and we're here to take care of you. That's nourishment.
01:06:14
Speaker
Helping patients move, helping them sleep. That's nourishment. And patients and families, I think, care deeply about things like sitting with them at the bedside, giving them, um you know, reassurance,
01:06:29
Speaker
giving them nutrition because they see it as a sign of healing and hope. And so I think we should care just as deeply about these small moments of nourishment as much as we do about life-saving technologies, if not more in many ways, about life-saving technologies or drugs. Because our goal, I i think, isn't simply just to help them survive a critical illness, but I think it's to help them recover, um,
01:06:58
Speaker
with strength, with the best quality of life possible, and more importantly, with just dignity.
01:07:06
Speaker
Well said, and thank you so much for a thoughtful discussion on such an important topic. And I really appreciate you sharing your time and your expertise with us and look forward to having you back on the podcast soon. Thank you so much.
01:07:23
Speaker
I really enjoyed our discussion.
01:07:27
Speaker
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01:07:41
Speaker
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