Protein requirements from health to ICU (short version) Disclosure. Payed lectures for Fresenius-Kabi, Baxter, Nestlé and Nutricia

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1 Protein requirements from health to ICU (short version) Olav Rooyackers Professor Department of Anesthesiology and Intensive Care Karolinska Institutet and University Hospital, Stockholm, Sweden Norsk Selskap for Klinisk Ernæring, Oslo 2017 Disclosure Payed lectures for Fresenius-Kabi, Baxter, Nestlé and Nutricia Consultant Fresenius-Kabi 1

2 Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU Protein Turnover Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool 2

3 Protein Synthesis Breakdown caspase calpain proteasome system autophagy/ lysosomal Adapted from Luo H et al. Cardiovasc Res 2009 Protein Turnover N-loss Diet Amino acid pool Amino acid 70g/dag 70g/dag oxidation 300g/dag Protein synthesis Protein breakdown Protein pool 3

4 Protein Turnover Diet Amino acid pool 70g/dag 300g/dag Protein synthesis N-loss 70g/dag Protein breakdown Amino acid oxidation Muscle (2 %/d) Intestine (40 %/d) Liver (25 %/d) Kidney (30 %/d) Skin (15 %/d) = 100 g/d = 80 g/d = 60 g/d = 30 g/d Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU Determining protein requirements RCT with Biochemical/physiological outcomes: Nitrogen balance Muscle or lean body mass Protein turnover Clinical outcomes: mortality, quality of life, muscle function 4

5 Nitrogen balance measurements N urine feaces sweat skin, hair N 0 Burns Injury Cystectomy Sepsis Hip replacement Malnourished Normal fasted gram N/70 kg Elwyn et al, Crit Care Clin 1987 Nitrogen balance measurements LIMITATIONS Accurate collection of all intakes and excretions needed Needs long measurement periods (days) Might need longer adaptation times Other losses possible (N 2 gas) Kidney and liver failure will influence measurements Only balance, no turnover 5

6 Larsson et al, Br J Surg 1990 Larsson et al, Br J Surg 1990 Protein Turnover Measurements Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool 6

7 Protein Turnover Measurements Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool Protein Turnover Measurements Diet Amino acid pool N-loss Tyr/CO 2 Amino acid oxidation Protein synthesis Protein breakdown Protein pool How we practically do this? 7

Protein requirements in health Protein requirements in the elderly

8 0h 3h 6h Tracer infusion (D5 and/or13cleu) TPN or Enteral Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU 8

9 All studies from WHO report Medline search Healthy and nitrogen balance (27 studies; 411 subjects) Individual data and 3 levels (19 studies; 271 subjects) 9

10 10

g/kg/day for 80 kg person 0.48-0.65 0.65-0.79 0.79-0.91 0.91-1.01 1.01-1.11 1.11-1.26 1.26-1.43 1.43-1.66 Biological value protein Protein Source Biological Value Egg, whole 93.7 Milk 84.5 Fish 76.

11 g/kg/day for 80 kg person Biological value protein Protein Source Biological Value Egg, whole 93.7 Milk 84.5 Fish 76.0 Beef 74.3 Soybeans 72.8 Rice, polished 64.0 Wheat, whole 64.0 Corn 60.0 Beans, dry 58.0 Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU 11

One epidemiological study showed a positive association between higher dietary protein intake and fewer health problems in older women.

12 Epidemiological studies and clinical trials support the need for higher protein intake by older adults. Several epidemiological studies have found a positive correlation between higher dietary protein intake and higher bone mass density; slower rate of bone loss; and muscle mass and strength. One epidemiological study showed a positive association between higher dietary protein intake and fewer health problems in older women. Several short-term metabolic studies investigated the differences in protein synthesis and breakdown (both whole-body and skeletal muscle) between younger and older adults. Given the complex nature of the aging process, it is not surprising that the combined results of these studies are inconclusive, and sometimes contradictory, for the fasted state. In the fed state, however, most researchers now agree that there is an impairment of the muscle protein anabolic response to meal intake in older adults, although some studies found no difference between older and younger adults Longer-term protein intake studies in older adults are scarce. In one intervention study of intermediate length, Campbell et al found 12

13 To help older people (>65 years) Epidemiological studies and clinical trials support the need for higher protein intake by older adults. Several epidemiological studies have found a positive correlation between higher dietary protein intake and higher bone mass density39e41; maintain slower rate and of bone regain loss42; and lean muscle body mass and strength.43 One epidemiological study showed a positive association between higher dietary protein intake and fewer health mass and function, the PROTproblems in older women.44 Several short-term metabolic AGE studies study investigated group the recommends differ-ences in protein synthesis and breakdown (both whole-body and skeletal average muscle) between daily younger intake and older at adults.45e47 least in Given the complex nature of the aging process,48 it is not surprising that the combined results of these studies are inconclusive, and sometimes contradictory, the for range the fasted state. of 1.0 In the to fed 1.2 state, g however, protein most researchers now agree that there is an impairment of the muscle protein anabolic response to meal intake in older adults,46,49,50 although some studies per found kilogram no difference between of body older and weight younger per adults day. Longer-term protein intake studies in older adults are scarce. In one intervention study of intermediate length, Campbell et al21 found Do elderly need more protein? From a scientific point of view, I do not see the convincing evidence 13

NO, from a scientific point of view, since I do not see the convincing evidence YES, from a

14 Prevent this rather than trying to fix this Anabolic resistance Anabolic threshold Age Wall et al, Plos One 2015 Do elderly need more protein? NO, from a scientific point of view, since I do not see the convincing evidence YES, from a general health perspective, since it might have a benefit for some elderly (frail, chronic disease) but it certainly doesn t harm 14

15 Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU 15

Disease Recommendation Evidence Intestinal failure We recommend that the protein and energy

intestinal absorptive capacity as estimated by ga

disease) and specific needs (e.g. acute illness, protein malnutrition), and that the adequacy of the regimen is regularly evaluated through clinical, anthropometric, and biochemical parameters.

16 Disease Recommendation Evidence Intestinal failure We recommend that the protein and energy requirements for CIF patients be based on individual patient characteristics (e.g. intestinal absorptive capacity as estimated by gastrointestinal anatomy and/or underlying disease) and specific needs (e.g. acute illness, protein malnutrition), and that the adequacy of the regimen is regularly evaluated through clinical, anthropometric, and biochemical parameters. We do not suggest the routine addition of individual amino acids (glutamine, cysteine, taurine) in the parenteral formula to decrease complications in adults on HPN. Many stable patients on HPN are satisfactorily maintained on pre-scriptions that provide g of protein Very Low Low Disease Recommendation Evidence CF The European Food Safety Authority (EFSA) recommends a population reference intake (PRI) of 0.83 g of protein/kg body weight per day in adults. Protein needs are likely to be higher for individuals with CF compared to non-cf individuals, i.e., 20% or more of macronutrient intake, consistent with protein intake needs for individuals with other inflammatory diseases - Disease Recommendation Evidence Burn injury Protein requirements, are higher than in other categories of patients, and should be set around g/kg in adults and g/kg/day in children. Glutamine. Currently, it is therefore difficult to recommend a precise dose, a route, or duration of administration. Currently, there is no evidence in the literature to recommend arginine supplementation in burn patients. Very Low (D) 16

17 Parenteral nutrition Disease Amount Evidence Acute Renal Failure Surgery (perioperative) Oncology Conservative therapy, mild catabolism Extracorporeal therapy, moderate catabolism CCRT, severe hypercatabolism (max. 1.0) g/kg/d Low (C) g/kg/d Low (C) Up to maximum 1.7 g/kg/d 1.5 g/kg ideal body weight Recommendation s range between a minimum amino acid supply of 1 g/kg/day and a target of g/ kg/day Low (C) Moderate (B) (Very Low (D)) Outline Protein metabolism Methods to study protein metabolism in humans Protein requirements in health Protein requirements in the elderly Protein requirements in disease Protein metabolism and requirement in the ICU Critical illness Disease Amount Evidence ESPEN (2009) ASPEN (2016) 17

18 Critical illness Disease Amount Evidence ESPEN (2009) When PN is indicated, a balanced amino acid mixture should be infused at approximately g/kg ideal body weight per day in conjunction with an adequate energy supply Moderate (B) ASPEN Larsson et al, Br J Surg 1990 Shaw et al, Ann Surg

19 Critical illness Disease Amount Evidence ESPEN (2009) When PN is indicated, a balanced amino acid mixture should be infused at approximately g/kg ideal body weight per day in conjunction with an adequate energy supply Moderate (B) ASPEN Protein requirements are expected to be in the range of g/kg actual body weight per day Very low (D) Weijs et al, JPEN 2012 Protein Protein and energy and target ICU 28d days Hospital Energy Energy target target ICU 28d days Hospital Hazard ratio for mortality Weijs et al, JPEN

20 Allingstrup et al, Clin Nutr 2012 Intervention studies Total nr studies 13 Randomized 4 Nitrogen balance 12 Turnover 3 Body composition 1 Amino acid profiles 1 Outcome 2 Protein Turnover Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool 20

21 Protein Turnover Diet Amino acid pool 70g/dag 300g/dag Protein synthesis N-loss 70g/dag Protein breakdown Amino acid oxidation Protein pool Protein Turnover with critical illness Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool Protein Turnover with critical illness Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool 21

22 Protein Turnover with critical illness Diet Amino acid pool N-loss Amino acid oxidation Protein synthesis Protein breakdown Protein pool 150 (µmol/kg/h) *** *** ns volunteers basal volunteers fed patients fed Rooyackers et al, Clin Nutr 2014 (µmol/kg/h) *** *** ns synthesis balance breakdown volunteers basal volunteers fed patients fed Rooyackers et al, Clin Nutr

23 Fractional Synthesis Rate (%/day) ICU group Control group 0 T lymphocytes MNC Leukocytes Tonsil Januskiewicz et al, J Clin Immun Albumin Liver FSR (%/day) Con SIRS ICU Con SIRS Barle et al, ICM 2001, Clin Sci 2006 (µmol/kg/h) *** *** ns synthesis balance breakdown volunteers basal volunteers fed patients fed Rooyackers et al, Clin Nutr

24 nmol/min/100ml leg * * Breakdown Balance Synthesis control fed septic fed Klaude et al, Clin Sci (µmol/kg/h) *** *** ns volunteers basal volunteers fed patients fed Rooyackers et al, Clin Nutr Net protein balance (mg/kg/h) Leu: r=0.80 : r= Parenteral amino acids (mg/kg/h) Rooyackers et al, Clin Nutr

190 (mg/kg/h) 7.0 6.0 5.0 4.0 3.0 Leu (mg/kg/h) 2.0 1.5 1.0 2.

25 synthesis breakdown balance oxidation Berg et al, Crit Care 2013 Oxidation Leu Oxidation p= p=0.190 (mg/kg/h) Leu (mg/kg/h) % 100% % 100% 2 Berg et al, Crit Care

26 13 C enrichment in arterial plasma 13 C enrichment in arterial plasma (APE) 1,1 0,9 0,7 0,5 0,3 0,1 Reference Patients 0, Time (minutes) Liebau et al., AJCN mg/kg/min * Breakdown Balance Synthesis * PN PN+EN PN PN+EN Volunteers ICU patients Liebau et al., AJCN Oxidation 5.0 (mg/kg/h) vol Vol. vol par basal ent. pat Pat. pat par basal ent. Liebau et al., AJCN

27 (umol/kg/h) Breakdown Balance Synthesis bas Glav bas Glav Week 1 Week 1 plus 3-4 days Liebau et al. Crit Care (umol/kg/h) Breakdown Balance Synthesis bas Glav bas Glav Week 1 Week 1 plus 3-4 days Liebau et al. Crit Care Oxidation umol/kg/h First Second Basal 1 2AA 3 Basal 4 5 AA Liebau et al. Crit Care

28 Protein turnover and feeding WB Protein net balance (µmol/kg/day) R² = Total AA intake (g/kg/day) nylalanine oxidation (µmol/kg/day) R² = Total AA intake (g/kg/day) CC. icu-metabolism.se Protein requirements from health to ICU Healthy >0.8 g/kg/day Elderly g/kg/day Disease Depends on disease but in general acute disease are recommended to get bit more: >1.0 g/kg/day ICU g/kg/day Burn g /kg/day Acknowledgement Jan Wernerman Lab Maria Klaude Brigitte Twelkmeyer Nicolas Tardif Eva Nejman Christina Hebert Towe Jakobsson Clinic Ramin Koucheck Agneta Berg Felix Liebau Inga Tjäder Lena Gamrin Anna Januskiewicz Åke Norberg Jonathan Grip Christina Blixt Martin Sundström Marie Smedberg Nurses Vivi Gustavsson Gunilla Herman Kicki Kilsand Sara Rydén Collaborators Urban Fläring Thomas Gustafsson Jamie Timmons Luc van Loon Folke Hammarqvist Bengt Isaksson Funding: SLL, VR, NIH, ESPEN, EU, ESICM 28

29 More info: 29

How to meet protein requirements in the ICU? Kate Fetterplace APD Senior Dietitian PhD Candidate

How to meet protein requirements in the ICU? Kate Fetterplace APD Senior Dietitian PhD Candidate Acknowledgments & Conflicts Supervisors and collaborators A/Prof Adam Deane A/Prof Christopher MacIsaac