1. Sarcopenia and Muscle Wasting on ICU, a dietetic perspective
Jessica Zekavica
Dietetic Lead for ICU, The Royal Surrey County Hospital
(Surrey Intensive Care Nutrition Collaborative)
Thank you for inviting me to talk about the dietetic perspective of sarcopenia in ICU.
This is a pretty big topic, and I am not going to be able to thoroughly explore our practice and the evidence base, and so my aim is to….
@SINCO_Nutrition

2. Aims
Introduce concepts and ideas being researched on ICU nutrition surrounding sarcopenia
(ii) Highlight how nutritional intervention is tailored to tackle sarcopenia and improve outcomes
My aims are to:
Introduce current concepts and ideas being researched at present.
Recognise the role that dietitians have in tackling this debilitating problem

3. Recap…
Sarcopenia is defined as: The progressive and generalized loss of skeletal muscle mass and strength, with risk of adverse outcomes
To recap briefly, here is the definition of sarcopenia.
Importantly, we are looking at not only reduced muscle mass but also reduced function

4. D1+2: ?permissive under-feeding D3+: meet targets, minimise deficits
So, considering a patients journey through ICU. This PICS model summarises this quite nicely.
Firstly, focusing on the initial phase. In a haemodynamically stable patient, days 1&2 would focus on introduction of low rate enteral nutrition. Benefits associated with this include: modulation of the stress response and maintenance of gut integrity.
One of the main reasons that some argue against full feeding in the first few days of ICU admission is because we cannot account for the endogenous glucose production.
It is thought that this, along with ‘full’ feeding leads to overfeeding and the subsequent detrimental consequences. However, endogenous glucose production can’t be measured at the bedside.
By day 3, there is a significant change in approach, and at this point, we should be meeting nutritional targets.
We know that whilst patients remain catabolic, they will continue to break down stores. Therefore we need to provide adequate nutrition to reduce/minimise this breakdown.
However, this approach makes certain assumptions…
Gentile et al, (2012)

5. The benefits of nutritional support
A recent review by Danni Bear et al highlighted quite nicely that the presumed benefit of nutritional support during critical illness in order to reduce muscle wasting is based on 3 assumptions:
That patients absorb all the nutrients delivered
That skeletal muscle can utilise all nutrients delivered
The consequence of these processes is an anabolic effect
In addition, as we know, not all patients are the same. Consequently, we need to be mindful of this when individualising nutritional care plans…..

6. The benefits of nutritional support
ABSORPTION
UTILISATION
ANABOLIC effect
A recent review by Danni Bear et al highlighted quite nicely that the presumed benefit of nutritional support during critical illness in order to reduce muscle wasting is based on 3 assumptions:
That patients absorb all the nutrients delivered
That skeletal muscle can utilise all nutrients delivered
The consequence of these processes is an anabolic effect
In addition, as we know, the ICU patient population is quite a heterogenous group. Consequently, we need to be mindful of this when individualising nutritional care plans…..
Bear et al (2017), Crit Care

7. Important to identify patients who benefit
most from nutritional support
Patients with NUTRIC score >5 : mortality reduces with increased caloric provision (Heyland et al, 2011)
NUTRIC
- Age
- APACHE II
- SOFA - Co-morbidities
Days from hospital to ICU
- IL6
This brings us to identifying those patients who will benefit most from nutritional intervention.
Selection of the correct patient groups for intervention is key.
In research, a score has been devised in order to screen ICU patients for nutritional risk. i.e. those who would benefit from aggressive nutritional therapy.
It is called the NUTRIC score, and takes in to account these factors: age, APACHE II, SOFA, patients comorbidities, days from hospital to ICU admission and IL6. Low risk is <5. High risk is >5.
However, it has been criticised that this is more of a disease severity
Using NUTRIC score, Heyland et al (2011) demonstrated that those patients with a high NUTRIC scores of 5 and above (i.e. malnourished patients- dotted line) had a lower probability of mortality with increased caloric nutritional provision.
Those patients with a low NUTRIC score (solid line) showed reduced benefit. And potential harm- Consider the EPaNIC trial. They found that supplementary PN to meet targets in the first 7days of admission led to greater muscle weakness.
In practice, this in theory, helps us target patients who we would be more proactive in nutritional provision and meeting estimated targets, and use more of our time/resources.
So, considering sarcopenia more specifically, how does nutrition fit in?

8. Early and rapid muscle wasting
Protein Catabolism
First of all, as we know, we witness early and rapid muscle wasting in our patients.
This article published in JAMA measured muscle protein turnover from days 1-7 of ICU admission. Measuring specifically, the percentage change in the rectus femoris muscle.
The left graph shows single versus multi organ failure, (ii) the right one sub-divides MOF further
Importantly, they identified a net catabolic balance despite an observed increase in muscle synthesis by D7. Generally, the more organs which are failing, the more severe the muscle wasting.
(Muscle synthesis was reduced on D1 and although normal on D7; muscle catabolism was high on D1 and D7).
Therefore we look towards nutritional interventions that will address this net catabolism i.e. reduce it and minimise losses
Puthucheary et al (2013), JAMA

9. What is “Optimum” provision?
So, what is the optimum nutritional provision?
This study averaged delivered nutrition throughout ICU admission and expressed it as a % of measured REE (on your left) and protein target (on your right)
The “U shaped curve” demonstrates approximately 70% of measured REE (when measured with a calorimeter) being the optimum caloric provision in terms of 60-day mortality.
This supported previous research by Heyland who identified <85% as optimal.
When the same data was interrogated for protein provision, authors found that protein intake was linearly associated with decreased mortality.
Note that target protein provision in this study was 1.3g/kg.
(ii) Here is a graph from a paper by Allingstrup et al (2012). They addressed the use of different protein targets. Protein provision was divided in to ranges of low, moderate and high. Low being 1.2g/kg/d and high being 1.5g/kg/d.
They showed that the more protein you give, the better % survival.

10. Outcome measures Sarcopenia is defined as:
The progressive and generalized loss of skeletal muscle mass and strength, with risk of adverse outcomes
How do we measure this?
But is percentage survival what we should be measuring?
To recap- sarcopenia is the loss of muscle mass and strength. We have adresssed the “adverse outcomes”. But is this outcome measure fit for purpose?
What about muscle function?
Another study by Ferrie et al found that those patients who received higher IV protein supplementation, had
Improved hand grip strength at day 7 (although not significantly)
Less fatigue than those given lower doses
Greater forearm muscle thickness on ultrasound.
BUT There was no difference in mortality….

11. Nutritional targets- the evidence
Calories
Protein
Calorimeter Vs
Equations
Protein profile?
So in summary, although there is consensus on caloric provision the question remains as to what is the optimum total provision.
In practice, calculation of requirements without a calorimeter is challenging- equations have been shown to have a degree of inaccuracy.
From a protein perspective, this also raises other questions with regards to the protein profile.

12. Produced with thanks from Danni Bear
This slide was provided by Danni Bear with thanks, and beautifully summarises the different protein ranges we are currently aiming for in different patient groups.
But what does “grams per kilo” mean in real terms??
Produced with thanks from Danni Bear

13. Mr Average  Take Mr Average: He is 70kg, over 50years old.
On the LEFT: He is fit and well and has a daily recommended value (DRV) of 0.75g/kg as per DOH. This is equivalent to = 52g protein/d or 1.5 chicken breasts.
On the RIGHT: He is sick and requires up to 2g/kg/d, totalling 140g or 4.5 chicken breasts……
These large doses are hard to deliver on ICU!!!
(Chicken breast= 31gpro)

14. Delivery of nutrition Supplementary feeding: - Enteral
- Parenteral (CALORIES)
- Reduced appetite
- Suppressed Ghrelin production
Increasing Delivery
Decreasing Delivery
(i) These high numbers are difficult to achieve in practice, when taking in to account feed breaks, intolerances or difficulties with route of delivery. We also have limitations when it comes to available feed products.
AND We know that even when patients can eat, they don’t eat enough.
Low appetite is predominantly identified as the main reason.
But this can be multifactorial. In addition, when looking in to Ghrelin, (the appetite hormone) in particular, it has been found that levels may not increase for up to 3weeks post ICU d/c (Nemanty et al. Critical Care 2006, 10:R10 )
(ii) So we need to focus on strategies to improve delivery.
There was some recent work done by Rowles et al who reviewed a small group of patients post ETT or trache. They found poor oral intake across the board, but more importantly, found that those patients who were also enterally fed actually had a non significant increase in appetite!
We need to be supplementing these patients either enterally. Or parenterally in high risk patients.
Observational studies have reported that feeding via the enteral route alone may lead to significant underfeeding- therefore the use of PN is on the rise.
Consider the CALORIES trial, they demonstrated we can do this safely.

15. Survivors OR Victims? Reduced QoL
Reduced capacity to live independently
Increased anxiety
Increased depression
51% not back at work within 1yr
Physical function below matched controls (1&5yrs
Reduced cognitive function
So coming back to our outcomes for intervention. A key focus during conferences and research has been whether we are creating survivors or victims?
Here I have listed the results of studies I found when researching this. Patient groups investigated included sepsis, ARDs- it is happening across the board.
There have been interesting findings from Needham et al. They followed up EDEN trial survivors.
Just to re-cap, the EDEN trial aimed to investigate trophic versus full enteral feeding in the first 6 days in patients with acute lung injury.
Needham found that EDEN trial survivors performed below predicted values for physical and cognitive performance at 6 and 12 months.
Whether they were fed trophic or full EN for the first 6days of admission- this did not affect results.
Of course, interpretation of these findings needs to be done with caution; for instance in the EDEN trial, patients only met 1.1g/kg of protein, critically appraising these papers and the authors methods,
However it begs the question of whether nutrition provides all the answers we are looking for and whether we are conducting the right research to get the answers we need….
*(EDEN trial: Initial trophic vs full enteral feeding in patients with acute lung injury-In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.)
Full feeding group only met 70% of targets, and each group only received 1.1g/kg of protein.

16. Rehab EXERCISE! Supplemental amino acids
Leucine enriched essential amino acids (EAA)
β-Hydroxy-β-Methylbutyrate (HMB)
EXERCISE!
Rehab
Returning to our patient journey on the “PICS” model
So far we have, focussed on the initial week to 10days of ICU admission.
Does this indicate that we need to consider what happens after those initial days?
What about rehabilitation?
Is it just about meeting protein and calorie targets- Attenuating muscle mass loss is one thing, but enhancement of muscle strength and function is another.
We also need to consider how we deliver nutrition as well as the profile of protein supplement being provided? Here are a couple of examples being currently researched.
As well as combined therapy with physiotherapy and physical activity.
Gentile et al, (2012)

17. To Summarise
Nutritional provision is vital to address protein catabolism and minimise losses.
We are yet to define what is optimal protein provision.
Early nutrition is important but not everything- we need to start thinking more long term.
Nutrition on its own is not the answer, we need to work collaboratively.
Nutritional provision is vital to minimise nitrogen imbalance and LBM loss.
We are yet to define what is optimal protein provision.
Early nutrition is important but not everything- we need to start thinking more long term.
And finally, even if we can reduce muscle wasting, this is not linearly linked with improved strength and function. We need to work collaboratively to achieve this.

18. References
Puthucheary et al. (2013) Acute skeletal muscle wasting in critical illness. JAMA. 310 (15), Ferrie et al. (2016). Protein requirements in the critically ill: a randomized controlled trial using parenteral nutrition. JPEN. 22 (4), Ramona et al. (2004). Two- year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med. 171, Iwashyna et al. (2010) Long- term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 304 (16), Needham etl al. (2013) Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. Am J respir crit care med. 188 (5), Gentile et al. (2012) Persistent inflammation and immunosuppression: A common syndrome and new horizon for surgical intensive care. Journal of Trauma Care Surgery. 72 (6), Allingtrup et al (2012) Provision of protein and energy in relation to measured requirements in intensive care patients. Clin Nutr. 31, Zusman et al (2016) Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study. Critical care. 20: 367 Heyland et al. (2011) Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. Critical Care. 15 (6), R268. Bear et al (2017) The role of nutritional support in the physical and functional recovery of critically ill patients: a narrative review. Critical care. 21: 226.