How to meet protein requirements

in the ICU?

Kate Fetterplace APD Senior Dietitian PhD Candidate

Supervisors and collaborators – A/Prof Adam Deane

– A/Prof Christopher MacIsaac

– A/Prof Jeffery Presneill

– Dr Audrey Tierney

– Dr Marina Mourtzakis

– Dr Adrienne Forsyth

– A/Prof Linda Dehehy

– Mrs Lisa Beach

– Ms Laura Knight

– Dr Thomas Rechnitzer

• Conflicts of interest: received honorarium / sponsorship support from Baxter, Fresenius Karbi, Nestle and Nutricia

Acknowledgments & Conflicts

• In healthy adults – balance between synthesis and breakdown

• During metabolic stress (major surgery, trauma) – imbalance occurs leading to net loss of body protein

• Regulated by pro-inflammatory modulators such as TNF-alpha and IL-6

Protein Metabolism

Muscle Protein

Muscle Breakdown

Muscle Synthesis

Amino Acids

Blood

Muscle

Amino Acids

Muscle loss occurs when

Muscle Breakdown > Muscle Synthesis

Protein Recommendations

McClave et al JPEN 2017, Singer et al Clin Nut 2009, CCPG Crit Care Nut 2015

SCCM & ASPEN 2016 ESPEN PN 2009 Canadian 2015

1.2-2.0g/kg actual body weight Likely higher in burn or multitrauma patients Quality: Low

1.3–1.5 g/kg ideal body weight Quality: Level B

Insufficient data to make a recommendation on the use of high protein diets in critically ill patients

• 113 critically ill patients – single centre

Provision of protein and energy in relation to measured requirements

Variable Unadjusted HR 95% CL

P value Adjusted for Age HR 95% CL

P value

APACHI II 1.10 (1.03-1.17) 0.003 1.08 (91.01-1.15) 0.03

Age 1.07 (1.03-1.11) <0.001 - -

Protein g/d 0.98 (0.96-0.99) 0.01 0.98 (0.97-0.99) 0.03

Energy kcal/d 0.99 (0.99-1.00) P =0.2 1.00 (0.99-1.00) 0.38

Allingstrup et al Clin Nutr 2012

Variable Low Protein (54g) (n= 37)

Medium Protein (84g) (n=38)

High protein (115g) (n=38)

Protein/kg/day mean (SD)

0.79 (0.29) 1.06 (0.23) 1.46 (0.29)

N balance g/kg per day mean (SD)

0.59 (0.48) -0.35 (0.41) -0.2 (0.58)

ICU Mortality n (%) 10 (27) 9 (24) 6(16)

Higher Protein Provision May Influence Survival

Allingstrup et al Clin Nutr 2012

• Morality between the high and low group was significantly different (p = 0.011)

• Survival probability: Low 49%, Medium 79%, High 88%

Protein delivery & clinical outcomes in the critically ill:

A systematic review and meta-analysis

Literature between 1966 and 2015

Inclusion criteria:

– RCTs comparing two different nutrition strategies for > 48hrs

– Reported a statistically significant difference in protein delivery (p <0.05)

– MV critically ill patients

– Outcome of mortality

Davies et al Criti Care & resus June 2017

• 14 studies including 3238 patients

• Mean protein delivered:

– Low mean (SD): 42.95 g/day (20.45) or 0.67g/kg/day (0.38)

– High mean (SD): 67.15 g/day (28.47) or 1.02g/kg/day (0.42)

• Lower protein had no influence on mortality OR 0.935 (Cl 0.72-1.22 p = 0.618)

Protein delivery & clinical outcomes in the critically ill:

A systematic review and meta-analysis

Davies et al Criti Care & Resus 2017

Professor Olav Rooijackers, Stockholm, Sweden

• Stable-isotope–labelled phenylalanine and tyrosine tracers

• Used to measure protein synthesis, breakdown and oxidation

• Critically ill patients are able to utilise extra enteral and parenteral amino acid to build new body protein

• Protein feeding yielded a detectable, although small, improvement in whole body protein balance

Amino Acid Tracers

Liebau F et al CC 2015, Liebau F et al. Am J Clin Nut 2015

Positive Protein Balance

Protein Balance Phe oxidation

• Conclusion: Protein intakes of

> 1.2 g/kg/day result in a positive protein balance

Synthesis WB Breakdown

Liebau et al. Critical Care (2015) 19:106

Protein Requirements in the Critically Ill: A RCT Using PN

• N = 120 Critically ill

• Aim: to deliver 1.2g/kg/day V. 0.8g/kg/day protein via PN – Delivered: 1.1g/kg Vs 0.9g/kg per day protein

– No difference in mortality (20% vs. 15%) p = 0.47

– Greater forearm muscle thickness:

• mean (SD): 3.2cm (0.4) vs 2.8 cm (0.4), p <0.0001

– Improved handgrip strength:

• mean (SD): 22 kg (10) vs 18.6 kg (12), p = 0.025

Ferrie et al JPEN 2016

Targeted Full Energy and Protein Delivery in Critically Ill Patients : A Pilot RCT

Fetterplace et al Unpublished data

60 MV critically ill enterally fed patients

Standard Care Intervention

Energy Target 25kcal/kg 25kcal

Protein Target 1.0g/kg 1.5g/kg

Formula 1.0kcal/ml standard 1.25kcal/ml high protein + Protein powder (6g bolus)

Delivery Method Hourly rate prescription

Volume prescription

• Pulse protein feeding patterns may enhance protein synthesis

• 25-30g protein per meal (containing 2.5-2.8g leucine)

• ‘Fast’ protein may have benefit over ‘slow’ proteins

• Proteins or amino acids are recommended in close proximity to exercise or activity

Optimise Muscle Protein Synthesis

Deutz et al Clin nut 2014, Bauer et al JAMDA 2013

• Leucine is an essential amino acid and has been shown to promote muscle protein synthesis

• Many amino acid preparations have been studied including BCAA (Valine, Leucine: isoleucine)

– Systematic review: 22 studies (4 in ICU & 18 muscle wasting condition)

• Leucine enriched EAA, HMB and creatine have shown some promising results in decreasing muscle loss in the critically ill

Optimal amino acids to maintain muscle mass

Wandrag et al J Human Nut & Diet 2014

Nutrition Interventions to Optimise Protein Provision

1

• High protein formula

• Enteral or Parenteral

2

• Protein Supplementation

• Enteral or Parenteral

3

• Volume based protocols

• Supplemental PN

Current High Protein Formula

Type Products Protein provided 25kcal/kg - 60kg

Enteral 1.25kcal/ml (Protein Plus, 63g/L) 75g (1.26g/kg)

1.0kcal/ml (Promote®, 62g/L) 93g (1.55g/kg)

1.3kcal/ml (Isosource® Protein Fibre, 67g/L)

75g (1.26g/kg)

Parenteral Olimel® (1.1kcal/ml, 56.9g/L) 77g (1.28g/kg)

Smofkabiven® ( 1.1kcal/ml, 50g/L) 68g (1.14g/kg)

Smofkabiven® HP (0.95kcal/ml, 63.6g/L)

100g (1.67g/kg)

Product Protein content Ingredients

Beneprotein® 6g protein per scoop

100% Whey protein

Protifar 2.2g protein per scoop

77% Casein 13% whey

Synthamin® 17 (10%) 50g/500ml IV balanced amino acid

Vamin® 18 (11.4%) 57g/ 500ml IV balanced amino acid

Current Protein Modular

What is the Optimal Formula?

• 60 yo male admitted following a MVA

• Head injury and multiple injuries and wounds

• Weight: 75kg BMI: 25

Nutrition Day 1 (Sedated)

Day 3 (Reduced Sedation)

Day 7 (No sedation commenced rehab)

Energy 20kcal/kg = 1500kcal 25kcal/kg = 1875 30kcal/kg = 2250

Protein 1.5g/kg = 112g 1.5g/kg = 112g 1.5g/kg = 112g

Optimal formula

1L (40ml/hr) Formula 1.5kcal/ml 112g protein

1.25L (50ml/hr) Formula 1.5kcal/ml 90g protein

1.5L (62ml/hr) Formula 1.5kcal/ml 75g protein

What is the Optimal Formula?

Optimal Enteral Formula For Critically Ill?

1000ml 1.5kcal/ml

Protein 95-100g/L

High quality protein – including

Whey protein

Osmolality 340-400

mOsmol/kgH20

With and without High quality fibre

Optimise Leucine content

and contain HMB

• What is the optimal protein provision?

–At present: 1.3-1.7g/kg per day

• What is the best type of protein?

• What is the optimal route for protein supplementation?

• How can we monitor protein adequacy ?

• Can these interventions improve functional outcomes and maintain lean body muscle mass?

Future Research

Thank you!