1.02/ Protein and Older Patients in the ICU

INTRO: Hello and welcome to Clinical Nutrition Notes, a podcast where we speak with guest experts and opinion leaders about the art and science of clinical nutrition, brought to you by Nestlé Health Science Canada. This podcast is intended for healthcare professionals for education purposes. I'm your host, Bethany Hopkins, Medical Affairs Manager with Nestlé Health Science.

Today, we'll be talking with Stuart Phillips about current concepts and protein for the older critically ill patient. Dr. Phillips is a PHD professor in kinesiology and adjunct professor in the school of medicine at McMaster University in Hamilton, Ontario. In addition, he's a tier-one Canada Research Chair in skeletal muscle health and director of the Physical Activity Centre of Excellence at the McMaster Centre for Nutrition Exercise and Health Research. Dr. Phillips’ research is focused on the impact of nutrition and exercise on human skeletal muscle protein turnover.

Hopkins: Thank you for joining us, Dr. Phillips. You published two review papers in 2017, one in Frontiers in Nutrition titled Current Concepts and Unresolved Questions in Dietary Protein Requirements and Supplements in Adults, the second in Nutrition in Clinical Practice titled Protein Turnover and Metabolism in the Elderly Intensive Care Unit Patient. I'd like to explore several concepts from these papers in the podcast. First, to set the stage, can you briefly describe body protein balance and how this changes in the older adult?

Phillips: Well first of all, thanks very much for having me on the podcast. I think the concept of protein balance in the way I describe it is probably best understood within the concept in trying to understand how a wall - that bricks are being put into, when bricks are simultaneously being taken out of - would change in size.

So, if you imagine that the patient's wall is their body protein, bricks or amino acids are being put into the wall in one process – in the case of muscle we call that muscle protein synthesis – and clearly the substrates would be all of the essential amino acids, but in particular the amino acid leucine. At the other end of the wall, bricks are being taken out and it's really a competition between those two processes as to which one wins that would determine the size of the protein-containing wall, and the one that we're most interested in – skeletal muscle. So, I think that that's the analogy that probably most best fits the situation.

And in the older ICU patient where an older person, prior to coming into the ICU, they're actually fighting a little bit of a losing battle because the wall is shrinking in size. In the case of an older person they would be undergoing the process of sarcopenia. So, the rate at which bricks are being taken out of the wall is exceeding the rate at which bricks are being put into the wall.

Hopkins: I love that analogy and actually I haven't heard anyone describe it quite like that before. Thanks, I think that helps describe the process really well for people. When you're talking about the older ICU patient – what age group are you referring to as an older adult?

Phillips: Yeah that's a good question. It's one that I'm cognizant that chronological age is the usual demarcation, but we actually believe that a person's, if you like, metabolic age prior to being admitted to the ICU might be important. So, somebody that is 60 years old and has a number of comorbidities, like for example diabetes or hypertension or heart disease, might be metabolically speaking a lot older than somebody who is 60 and in quite good shape. But nonetheless, we use 60 or 65 as the usual demarcation to say that this person is definitely older and experiencing some kind of reduction, at least in their muscle mass, probably prior to being admitted to the ICU.

Hopkins: And when you think about that age range, and the typical medical, surgical ICU patient, most often, a majority of those patients, maybe two thirds, are over the age of 60. And many of them do have multiple comorbidities, so this is really a demographic that clinicians across the country are working with day in and day out. So, with that older adult and the challenges they have, you said, in terms of building that wall, what happens when you layer in critical illness on top of this? It's been reported in the older, critically ill patient that they do represent a greater challenge, and you've used the term “perfect storm” to describe the loss of lean mass in these older ICU patients. Can you explain what you mean by this perfect storm?

Phillips: Sure. I think that what you have to appreciate is that somebody who's 60 is probably – no matter whether they're metabolically healthy or not – they're experiencing a loss of muscle mass prior to entering the ICU. That's the normal age-related loss of muscle due to sarcopenia. And then when you layer on top the disuse that is associated with the ICU – so most of these patients are on bed rest for a period of time – and you consider all the factors that are going on in the ICU in the case of undernutrition, what we call an anabolic resistance – in other words – an older person is unable to mount a robust protein synthetic response. We've got procatabolic cytokines. We've got procatabolic hormones, cortisol for example. These things all come together to form a confluence of factors that would really predispose that older ICU patient to losing not just body protein mass but in particular muscle mass.

Hopkins: Thinking about the challenges and the confluence that you're talking about, that the older, critically ill patient may experience. In order to mitigate or lessen muscle loss or lean tissue loss, you've suggested that there needs to be an aggressive and an early intervention. What kind of early interventions are you referring to here Dr. Phillips?

Phillips: Well, I think the most important one would be to consider how soon and how early you can get nutrition on board. So for a lot of ICU patients, until there's a feeding tube in place for example, these patients might remain NPO which would be a serious situation where you're, again because of what we call an iatrogenic undernutrition or, if you like, an ICU malnourishment would result in an inability of amino acids to get on board, and it would actually aid in some of the really rapid muscle loss that we see.

So, the biggest thing is to get amino acids and protein on board as soon as possible via the enteral route or if not, by the parenteral route as possible. It's not always easy, I understand that, but the earlier that those amino acids can be put into circulation and available to support the synthetic side of the wall building, if you like, the better.

Hopkins: Yeah. And I think that's a challenge sometimes for clinicians in terms of not having a crystal ball and knowing how long is this person going to be NPO and unable to consume nutrition orally. So getting on with nutrition support, whether it be enteral or parenteral nutrition, may be something that needs to be considered sooner and then can be adjusted depending on what happens with the course of that individual.

When we're thinking about the protein that's being delivered to ICU patients, a lot of times the dosing is what first comes to mind for individuals, or how much protein does my does my patient require? When you're talking about muscle protein synthesis and anabolic resistance, what protein dosing appears to be necessary to really have an impact on protein synthesis in the older patient?

Phillips: Yeah that's a great question, and I think it's important for me to emphasize here that as part of the paper that I published in association with the Nutrition in Clinical Practice, there was a consensus paper that was published in association with that that invited not just myself but a number of other panelists to comment on this.

And the general consensus, so not just my own recommendation, was that should be aiming for at least 1.2 grams of protein for kilo per day, and upwards maybe in the older ICU patient to 1.5 or 1.6 or even greater in some situations. Maybe as high as 2 grams per kilo per day.

So, it's definitely not a hard and fast number, but I think the general consensus was we need to come to at least 1.2, better if it's 1.5 or 1.6, and it may need to be in the older patient as high as 2 grams per kilo per day.

Hopkins: Depending on the degree of catabolism and what else is happening, the older ICU patient would be managed differently than the older individual living in the community or with chronic illness.

Phillips: I think that the important distinction is if someone is in the community versus someone who is in the ICU is the ability to be physically active and mobile. In addition to obviously provision of protein, being physically active or able to bear some type of load with your muscles and do some form of physical activity, even if it's just going for a walk, would be beneficial. That's part of the second half of the equation in ICU patients is to, as soon as they are able, try and get them mobile. That could include mobility as little as sitting at the bedside or even standing for a period of time. But certainly, trying to get patients to be mobile earlier rather than having a prolonged period of bed rest.

Hopkins: And I think more and more people are beginning to realize that this combination of activity, whatever that activity may be, and providing exogenous protein seems to be really important. When you're talking about protein dosing and why that's important, another area that you addressed in your publications is the quality of protein and that that can also have an impact on clinically relevant outcomes. Yet that particular aspect of protein nutrition may often be underappreciated. And I’m wondering if you can talk for a minute about what do you mean by protein quality and the impact that this may have for the older patient?

Phillips: Yeah, I think you're right, protein quality is really something that's been, I don't know about unappreciated but maybe underappreciated. One of the things that's becoming clear with research that we've done, and a number of other labs as well, is that the essential amino acids – so it's the nine of the 20 amino acids that we need to have – unto themselves has subclasses and subcategories that are important to have. And, so a protein, if you're going to feed it, needs to obviously have the full complement of essential amino acids and be easily digestible, and that's traditionally how we've referred to protein quality – so good digestibility, good essential amino acids.

What's emerging now is that the content of a single amino acid, one of the branch chains leucine, is particularly important. And, if you like, it's a substrate. So, it's a brick for building new muscle protein, but it's also the brick that sort of gets the process going. In other words, when leucine gets delivered it's a big trigger signal to initiate the process of protein synthesis. So, quality of proteins is important to consider with respect to all of the essential amino acids but in particular the quantity of leucine that is in a protein would be I think really critical to consider.

Hopkins: As we're talking about proteins and looking at essential amino acids, in particular leucine, which proteins are you are you referring to here, Dr. Phillips, that would be rich in leucine content?

Phillips: The proteins that top the list in terms of leucine content are dairy-based proteins. And whey in particular is a very rapidly digested, high leucine-containing fraction of about 20 percent, of milk protein. And it's really the one that is the gold standard and highest leucine-containing, positive protein control that we have.

So, formulations that are based in whey protein or milk protein in particular would probably be particularly important. Not that other protein sources aren't good. But if you wanted to rank them, then it would be whey protein right at the top and then downwards from there.

Hopkins: Thank you for clarifying that. Now getting to the last couple of questions. A question that often comes up, or a concern for clinicians when we're talking protein, is protein and renal function. The kidney is an organ intimately involved in protein metabolism, and there is a concern that higher protein intakes could have adverse effects on a patient's renal function. What does the research tell us about higher protein intakes and kidney function in general and/or in the in the ICU setting?

Phillips: That's an excellent point. And I think it's important to draw a sharp distinction between people who have pre-existing renal conditions and people who are in the ICU without any indication of renal dysfunction. And the important point probably to make is that these people need to survive the ICU, and we know that early provision and greater levels of protein help older patients. And so, I think that that's the lens through which I view this question and place my answer in context.

So, if somebody is known to have some pre-existing renal condition, and they don't have good renal function then it probably isn't a good idea to load up on protein. But, at the same time, observational studies suggest that protein intakes at least greater than 1.2 g/kg during critical illness improve ICU survival compared with lower protein intakes. And if you look at the combined potential to achieve a positive, whole-body balance of protein with much higher intakes in older patients, then I'm going to borrow a line from Dr. Rollie Dickerson, who is one of the preeminent physicians in this area where he says, “the limitation of protein intake on a short-term basis doesn't appear to be warranted in a patient without overt kidney failure or a contraindication for hemodialysis.”

And really the point is that the negative impact of withholding or giving lower protein would be greater than considering what impact that would have on a patient's kidney function unless the clinician has full-blown knowledge that it’s compromised to some degree.

Hopkins: You bring up a good point. I know Roland Dickerson has been cited in that area a couple of times and in publications, and the whole concept of contraindications and dialysis I think is important for clinicians to consider, because many patients in the ICU would also be being dialyzed.

One last item would like to talk about before we close, is about the role of protein affecting outcomes beyond mortality. Mortality is obviously an important outcome, but other outcomes such as quality of life and functional status are beginning to be recognized as things that we need to understand a little bit more. These outcomes really matter to patients and families. And there's emerging evidence about the importance of continued vigilance in ensuring proper nutrition and exercise after people leave the ICU. Can you comment for a minute on that, Dr. Phillips?

Phillips: Yeah, I think what's particularly important for people to realize is the rate of survival in ICU patients now is at an all-time high, but it shows in that data or trending that survival rates are going to go up. That combined with the fact that as you mentioned about two thirds of ICU patients are probably over the age of 60 or 65. You've really got a confluence of two things coming together where you've got a high survivability rate, you've got a majority of older patients, and you're really talking about improving the quality of lives of these patients afterwards.

And the biggest condition that I think people need to be aware of is an ICU-acquired muscle weakness, and this is a downstream corollary or consequence of the loss of lean mass and the loss of physical conditioning that is associated with prolonged periods of bed rest and time spent in the ICU. So, the longer that bed rest and the longer that ICU stay, then clinicians really need to be aware of what it would take for this person to return home, return back to work and return back to the good quality of life, able to perform activities daily living.

So, there's support for rehabilitation after the ICU and good physical function and then obviously good management of muscle mass and, as much as possible, physical therapy during the ICU is going to be critical.

Hopkins: This is helping to set the stage for what's happening in that recovery period in the weeks and months to follow an ICU admission, with nutrition and exercise. As someone who is very interested in nutrition to begin with, it's really fascinating to see how our understanding of what's happening with protein nutrition has evolved. In the last decade alone, there's been considerable advances, and it's really encouraging as well to hear from some of the work that you're doing and others, that older individuals can increase protein synthesis, provided in part that they're receiving sufficient dosing of quality protein and, as you mentioned, also considering that exercise or activity component.

Before we sign off, I'd just like to take a minute to ask you one last question, so our listeners can get to know you a little more. Since we've been talking about nutrition this podcast, can you tell us how you first became interested in the field of nutrition?

Phillips: Yeah, it's a good question. I was late arriving to my sort of epiphany moment and literally – I mean I don't know that it was a single moment, but it was it was definitely a course in the last semester of my fourth year – and I did an undergraduate degree in biochemistry during the age of, I'll call it gene therapy 1.0, where we were going to deliver genes to patients and we were going to cure all kinds of diseases.

And I got into biochemistry with that on my mind thinking that this was going to be in the future. And then in the last semester of my fourth year I took a course in nutrition with Dr. Stephanie Atkinson, and perhaps a few of your listeners know Stephanie, and I'll be honest I go right on the record as saying is that she opened my eyes. I was absolutely blown away by the things I learned, and my life kind of turned on a dime. At that moment I decided that that was something I really liked and really enjoyed and pursued a master’s with Steph and went on from there. So, yeah, one single course in the fourth year that was sort of an elective slot was really the turnaround for me.

Hopkins: It's interesting isn't it how your life can take such a different direction - and just by taking an elective course? So, thank you so much for sharing that. I hadn't heard that background before, Dr. Phillips.

On that note we'll conclude the podcast and I'd like to thank you for joining us and thank all of our listeners.

CLOSING: This concludes our episode of the Clinical Nutrition Notes podcast.

To listen to more podcasts or to subscribe to Clinical Nutrition notes, visit our website at NestleHealthScience.ca.

For the Nestlé Health Science podcast team, I'm Bethany Hopkins.