Proteins Amino Acids. K. Georg Kreymann Baxter Healthcare, Deerfield, USA

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1 Proteins Amino Acids K. Georg Kreymann Baxter Healthcare, Deerfield, USA

2 François Magendie ( )

3 Manfred Köhnlechner ( ) The Manager Diet

4 Main points Arginine supplemented diets should be given perioperatively in GI and non-gi surgery. Leucine and other branched-chain amino acids are stimulating protein synthesis in cancer patients. The demand for energy and protein varies with different diagnoses and also with the time course of the disease A balanced approach means to feed each patient the right amount of energy and at the same time the right amount of protein

5 Amino Acids Which kind of amino acids? How much energy and protein? What means balanced?

6 Amino Acids under Special Discussion Glutamine Arginine Leucine (and other branched-chain AAs)

7 JAMA 2001

8 Immunonutrition in the Critically Ill Heyland KD et al. JAMA 2001 Effect on Mortality Elective Surgical Patients Daly et al Daly et al Braga et al Schilling et al Gianotti et a Senkal et al Braga et al Senkal et al Snydermann et al Critically Ill Patients Cerra et al Gottschlich et al Brown et al Moore et al Bower et al Kudsk et al Abbott Laboratories 1995 Engel et al Mendez et al Rodrigo et al Weimann et al Atkinson et al Gaban et al Besser Schlechter Pooled Risk Ratio 0,001 0,01 0,

9 Immunonutrition in the Critically Ill Heyland KD et al. JAMA 2001 Elective Surgical Patients Daly et al Daly et al Braga et al Schilling et al Gianotti et a Senkal et al Braga et al Senkal et al Snydermann et al Besser Schlechter Effect on infectious complications Critically Ill Patients Cerra et al Gottschlich et al Brown et al Moore et al Bower et al Kudsk et al Abbott Laboratories 1995 Engel et al Mendez et al Rodrigo et al Weimann et al Atkinson et al Gaban et al Pooled Risk Ratio 0,01 0,

10 Immunonutrition in the Critically Ill Heyland KD et al. JAMA 2001 Elective Surgical Patients Daly et al Daly et al Braga et al Schilling et al Gianotti et a Senkal et al Braga et al Senkal et al Snydermann et al Besser Schlechter Effect on length of hospital stay Critically Ill Patients Cerra et al Gottschlich et al Brown et al Moore et al Bower et al Kudsk et al Abbott Laboratories 1995 Engel et al Mendez et al Rodrigo et al Weimann et al Atkinson et al Gaban et al Pooled Risk Ratio

11 American College of Surgeons 2011

12 Effect of arginine-supplemented diets on infections Drover JW et al. American College of Surgeons 2011

13 Effect of arginine-supplemented diets on hospital length of stay Drover JW et al. American College of Surgeons 2011

14 Effect of arginine-supplemented diets on mortality Drover JW et al. American College of Surgeons 2011

15 Results of Subgroup Analyses Drover JW et al. American College of Surgeons 2011

16 Amino Acids under Special Discussion Glutamine Arginine Leucine (and other branched-chain AAs)

17 Clinical Nutrition 2011

18 Muscle Protein Fractional Synthetic Rate Deutz NEP et al. Clinical Nutrition 2011

19 Clinical Nutrition 2013

20 Change in Total Lean Mass over 10-day Bed Rest Deutz NEP et al. Clinical Nutrition 2013

21 Clinical Nutrition 2006

22 Rates of Leg Muscle Glutamine Synthesis Biolo G et al. Clinical Nutrition 2006

23 Conclusion I Arginine supplemented diets given perioperatively reduce the infection rate and shorten the hospital length of stay in GI and non-gi surgery. Leucine and other branched-chain amino acids are stimulating protein synthesis in cancer patients.

24 Amino Acids Which kind of amino acids? How much energy and protein?

25 The Energy/Nitrogen Ratio Is based on the idea that any consumption of protein has to be accompanied by certain amount of nonprotein calories to guarantee its anabolic use To guarantee an optimal utilization of amino acids a sufficient amount of non-protein energy should be added. Under conditions of normal metabolism a ratio of 130:1 to 170:1 (kcal/g N) is recommended (A). DGEM Guidelines Parenteral Nutrition 2007 Amino Acids

26 Resting Metabolism and Nitrogen Excretion Resting Metabolism (%) Nitrogen Excretion (g/day) Major Burn Major Burn Peritonitis Skeletal Trauma Fracture Days x 1.8 Severe Sepsis Elective Op x 3.0 Long CL et al, JPEN 1979

27 Retrospective analysis of the energy/nitrogen ratio in different diseases Design Method Review of the literature of the past 50 years Included were all studies that measured energy expenditure and nitrogen loss in the same patients at the same time (53 studies on 1107 subjects in 91 cohorts) Evaluation The energy expenditure was correlated with the nitrogen resp. protein loss Three classes of protein loss were set up Kreymann G et al, Clinical Nutrition 2012

28 Cohorts with a very low protein loss (<0.8 g/kg) Author Year Patients n weight REE activity TEE UUN UN Nins total N Protein/ E/N /kg factor /kg /kg /kg /kg /kg kg ratio healthy men, Steiniger obese Long C 1981 controls Steiniger 1985 healthy men Ward 1986 GI surgery, placebo Long C 1979 controls Ward 1986 GI surgery, GH Selldén 1998 hysterectomie Nelson KM Bessey 1995 controls volunteers, epineph Calloway 1975 healthy volunteers

29 Cohorts with a very low protein loss (< 0.8 g/kg) Author Year Patients n weight REE /kg activity factor TEE /kg UUN /kg UN /kg Nins /kg total N /kg Protein/ kg Long C 1981 controls Steiniger 1985 healthy men, obese E/N ratio Calloway 1975 healthy volunteers Nordenstr öm 1983 acutely ill, glucose system Long C 1979 controls Chikenji 1987 Selldén 1998 Nelson KM malnourished patients hysterectomie, post OP controls

30 Cohorts with a moderate protein loss (0.8 <1.2 g/kg) Author Year Patients n weight REE/kg activity E/N TEE/kg UUN/kg UN/kg Nins/kg total N/kg protein/kg factor ratio Ward 1987 GI surgery, GH Steiniger 1985 healthy men, normal Burge 1994 obese patients, Nelson KM 1995 femoral neck fracture Selldén 1998 hysterectomie Nordenström 1983 acutely ill Whitehead 1996 healthy subjects Iapichino G 1982 malabsorption Burge 1994 obese patients Richards EW 1993 lung cancer Greig 1987 sepsis, high protein Elia 1990 healthy men Richards EW 1993 controls Müller MJ 1993 Crohn s disease b Fernandez 1993 surgical pats Dullo 1996 healthy men Akrami 1980 mitral valve replac Black 1997 healthy men Eden E 1984 cancer Black 2000 healthy women Black 1997 healthy women Mann S 1985 surgical critically ill Mingrone 1998 controls Müller MJ 1993 Crohn s disease a Greig 1987 sepsis, low protein Ratheiser 1998 healthy men

31 Cohorts with high protein losses (>1.2 g/kg) Author Year Patients n weight REE/kg activity factor TEE/kg UUN/kg UN/kg Nins/kg total N/kg Charlin 2002 HIV-infection Hunter 1988 surgical critically ill Iapichino G 1981 trauma critically ill mod Protein /kg E/N ratio Black 1997 post-obese subjects Long C 1979 blunt trauma Mingrone 1998 Crohn's disease Schmitz 1981 surgical ICU patients Borzotta 1994 isolated head injury Serog 1983 Burns Frankenfield 1997 trauma critically TC Long C 1979 Sepsis Long C 1979 Burns Frankenfield 1997 trauma critically NP Bruder 1991 head trauma Frankenfield 1997 trauma critically HC Borzotta 1994 closed head injury Scheinkestel 2003 critically ill, CRRT Schmitz 1981 surgical ICU patients

32 Cohorts (%) Total Protein Loss Total Protein Loss (g/kg BW/day) Kreymann G et al, Clinical Nutrition 2012

33 60 Scatterplot: total protein loss (g/kg) TEE (kcal/kg) vs. (MD fallweise) Protein Loss TEE (kcal/kg) and total protein loss (g/kg) = Total Energy * Expenditure Korrelation: r = TEE (kcal/kg) TEE (kcal/kg ) r= total protein loss total protein loss (g/kg) 95% Konfidenzintervall

34 E/N ratio E/N ratio Protein Loss and E/N Ratio total protein loss (g/kg) total protein loss (g/kg) Kreymann G et al, Clinical Nutrition 2012

35 Conclusion II The energy/nitrogen ratio varies in different nutritional situations It decreases with increasing loss of protein Therefore, not all patients can be fed with the same formula The energy/nitrogen ratio in triple chamber bags should be adjusted to these different nutritional situations

36 Amino Acids Which kind of amino acids? How much energy and protein? What means balanced?

37 Case report A male patient, 64 years body weight 82 kg, height 184 cm diagnosis: multiple trauma current status: 5 th day post OP, temperature up to 39.6 C, bilateral pneumonia measured energy expenditure: 2,200 kcal (26.8 kcal/kg) measured nitrogen loss: 19.7 g equivalent to 123 g protein ( 1.5 g protein/kg)

38 Case report A - Recommendation measured energy expenditure: 2,200 kcal measured nitrogen loss: 19.7 g ( 1.5 g Protein/kg) matches an EE/N-ratio of 112 recommendation: triple chamber bag with 1,070 kcal/l and 57 g AA/l (EE/N=119) volume to cover energy expenditure: 2,200/1,070 = 2.1 l corresponds to an administration of amino acids: 2.1 * 57 g = 120 g 1.46 g/kg

39 Case report A unbalanced therapy measured energy expenditure: 2,200 kcal measured nitrogen loss: 19.7 g ( 1.5 g Protein/kg) EE/N-ratio: 112 e.g. triple chamber bag with 1,140 kcal/l and 44 g AS/l (EE/N=163) volume to cover energy expenditure: 2,200/1,140 = 1.9 l corresponds to the administration of amino acids: 1.9 * 44 g = 83,6 g 1.0 g/kg g/kg

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41 Case report A unbalanced therapy (II) measured energy expenditure: 2,200 kcal measured nitrogen loss: 19.7 g ( 1.5 g Protein/kg) EE/N-ratio: 112 volume to cover protein needs: 123 /44 = 2.8 l 1.5 g/kg corresponds to an energy supply: 2.8*1,140 = 3,190 kcal kcal ml

42 Case report B female patient, 42 years body weight 56 kg, height 162 cm diagnosis: short bowel syndrome hysterectomy current status: 3. day post OP, no fever, no complications Pat. is in a stable condition measured energy expenditure: 1,350 kcal (24.1 kcal/kg) measured nitrogen loss: 9.0 g equivalent to 56 g of protein ( 1.0 g Protein/kg)

43 Case report B - Recommendation measured energy expenditure: 1,350 kcal measured nitrogen loss: 9.0 g ( 1.0 g Protein/kg) matches an EE/N-ratio of 150 recommendation: e.g. triple chamber bag with 1,140 kcal/l and 44 g AA/l (EE/N=163) volume to cover energy expenditure: 1,350/1,140 = 1.2 l corresponds to the administration of amino acids: 1.2 * 44 g = 53 g 0.94 g/kg

44 Case report B unbalanced therapy measured energy expenditure: 1,350 kcal measured nitrogen loss: 9. g ( 1,0 g Protein/kg) EE/N-ratio: 150 e.g. triple chamber bag with 1,070 kcal/l and 57 g AA/l (EE/N=119) volume to cover energy need: 1,350/1,070 = 1.3l corresponds to an administration of amino acids: 1.3 * 57 g = 74.1 g 1.3 g/kg +0.3 g/kg

45 Case report B unbalanced therapy (II) measured energy expenditure: 1,350 kcal measured nitrogen loss: 9.0 g ( 1.0 g Protein/kg) EE/N-ratio 150 volume to cover protein needs 56/ 57 = 1.0 l 1.0 g/kg corresponds to an energy supply: 1.0*1,070 = 1,070 kcal -300 kcal

46 What means balanced? Only a balanced approach can provide the right amount of energy and protein at the same time

47 Conclusion Arginine supplemented diets should be given perioperatively in GI and non-gi surgery. Leucine and other branched-chain amino acids are stimulating protein synthesis in cancer patients. The energy/nitrogen ratio varies in different nutritional situations For a balanced provision of energy and nitrogen, triple chamber bags with an adequate energy/nitrogen ratio should be used

48 Thank you for your attention!