Amino acids: the forgotten building blocks? Vanessa Kotze RD(SA) Lecturer: Dpt of Human Nutrition

Transcription

1 Amino acids: the forgotten building blocks? Vanessa Kotze RD(SA) Lecturer: Dpt of Human Nutrition

2 Focus of presentation Adult critical illness Each amino acid Protein synthesis properties Evidence Guidelines Recommendations

3 Introduction ICU acquired weakness impaired weaning from ventilator increased mortality Altered amino acid (AA) metabolism contributing factor: Gluconeogenesis Acute phase protein synthesis Non essential AA becomes conditionally essential AA Result: loss of lean body mass (LBM) Muscle fibres: atrophy & degeneration Decreased myofibrillar size Gunst J 2018

4 Introduction Will increased AA administration prevent muscle weakness? 3 RCT: absence of clear benefit Possible reasons Amino acid-induced suppression of autophagy (degree = amount) Failure to counteract net catabolism Wrong amino acid composition Is EAA the key? Gunst J 2018

5 Specialised AA Amino acids EAA Conditionally EAA Non EAA Leucine Arginine Glutamine Citrulline Taurine

6 Specialised AA Amino acids EAA Conditionally EAA Non EAA Leucine

7 Leucine Functions Insulin secretagogue For protein synthesis = need activation of initiation factors Act as neutraceutical to activate Possibly assist with protein synthesis? Inconsistent theory = availability of all EAA Wolfe RR 2017

8 Leucine Interest in BCAA date back to 1980 s Stimulate prot synth & muscle prot catabolism Frank Cerra: BCAA-PN in surgical patients: levels of plasma levels of BCAA and arginine Improve N balance (promoting prot synth) prelab levels lymphocyte count But what about clinical outcomes? Moore FA 2017

9 Leucine Clinical outcomes Did not demonstrate any effect on mortality or other parameters Expensive Result: interest faded Moore FA 2017

10 Recommendations ASPEN 2016 Based on expert consensus, we suggest that standard enteral formulations be used in ICU patients with acute and chronic liver disease. There is no evidence of further benefit of branched-chain amino acid formulations (BCAA) on coma grade in the ICU patient with encephalopathy who is already receiving first-line therapy with luminal-acting antibiotics and lactulose Taylor 2016

11 To supplement or not to supplement? Possible role Elderly Persistent inflammation, immunosuppression and catabolism syndrome (PICS) Problems Lack of info on use (clinical setup and EN/PN)

12 Specialised AA Amino acids EAA Conditionally EAA Non EAA Arginine

13 L-Arginine Promotes T-lymphocyte & fibroblast proliferation Intracellular substrate for NO production in macrophages Improve bactericidal activity Secretagogue: growth hormone Prolactin Somatostatin Insulin Glucagon Moore FA 2017

14 Arginine metabolism Myeloid cells Limiting amino acid Ochoa Gautier JB 2017 Pierre 2013

15 So what? arginine requirements sense levels Reduced protein synthesis Dec wound healing suppressed lymphocyte proliferation: Dec immune function Ochoa Gautier JB 2017

16 To supplement or not to supplement? Trauma, surgery, chronic infections clinical infections & complications LOS in hospital ventilator days x no effect on mortality PICS possibly Moore FA 2017 Pierre 2013

17 Arginine metabolism Ochoa Gautier JB 2017 Pierre 2013

18 To supplement or not to supplement? Upregulation of inducible nitric oxide (NO) synthase Arg = suppresses lymphocyte proliferation Citrulline, NO Inc NO Pathological vasodilation - amplifying shock Physiologically possible but clinically unproven,? relevant Moore FA 2017

19 Recommendations: EN ASPEN 2016 We suggest immune-modulating enteral formulations (arginine with other agents, including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], glutamine, and nucleic acid) should not be used routinely in the MICU. Consideration for these formulations should be reserved for patients with TBI and perioperative patients in the SICU. Canadian, 2015 We do not recommend diets supplemented with arginine and other select nutrients be used for critically ill patients Taylor 2016

20 Recommendations: EN ESPEN, 2006 Immune-modulating formulae (formulae enriched with arginine, nucleotides and x-3 fatty acids) are superior to standard enteral formulae: in elective upper GI surgical patients in patients with a mild sepsis in patients with trauma

21 Specialised AA Amino acids EAA Conditionally EAA Non EAA Arginine Glutamine Citrulline Taurine

22 Glutamine Substrate for renal ammoniagenesis Precursor for glutathione (AOX) Major fuel for rapidly dividing cells Enterocytes Colonocytes = intestinal mucosa integrity Immune cells McCarthy 2018 Gunst 2018

23 What happens with gln in crit illness? gln levels surgical trauma, major injury, burns, infections, and pancreatitis dysfunction Hypothetically it should help preserve muscles when supplemented? BUT this is not the case Proteolysis: Rather controlled by degree of inflammation Not by glutamine levels Additional amino acids are oxidised: limited synthesis McCarthy 2018

24 Is it safe to use? Nu of trial last few years Mortailty In hospital; 6 months post discharge No benefit: infection McCarthy 2018

25 What does the evidence say? Varying results from studies EN gln: Systematic review 2015, van Zanten 1079 critically ill patients No effect on Hospital mortaility Infectious complications ICU LoS Significant reduction: hospital LoS McCarthy 2018

26 What does the evidence say? EN & PN gln: Systematic review 2014 Tao et al Moderate evidence infectious complications days mechanical ventilation Low evidence: hospital LoS Critically ill & surgical McCarthy 2018

27 What does the evidence say? Meta analysis, Oldani et al RCT, 3696 ICU patients Control vs experimental group No difference in Hospital mortality ICU mortality Infections McCarthy 2018

28 What does the evidence say? Meta analysis: Stehle P 2017 PN gln-dipeptide administration Inclusion: critically ill patients No hepatic / renal failure Hemodynamically & metabolically stable Adequate nutrition Gln according to guidelines Stehle P 2017

29 Recommendations: Enteral gln ASPEN, 2016 The addition of enteral glutamine to an EN regimen (not already containing supplemental glutamine) should be considered in burn, trauma, and mixed ICU patients (Grade B). Canadian, 2015 We recommend that enteral glutamine NOT be used in critically ill patients. Taylor 2016

30 Recommendations: Enteral gln ESPEN, 2006 Glutamine should be added to standard enteral formula in burned patients trauma patients There are not sufficient data to support glutamine supplementation in surgical or heterogenous critically ill patients

31 Recommendations: Parenteral gln ASPEN, 2016 We recommend that parenteral glutamine supplementation NOT be used routinely in the critical care setting. (moderate) Canadian, 2015 We recommend parenteral supplementation with glutamine NOT be used. There are insufficient data to generate recommendations for intravenous glutamine in critically ill patients receiving enteral nutrition: Do NOT use Taylor 2016

32 Recommendations: Parenteral gln ESPEN When PN is indicated in ICU patients the amino acid solution should contain g/kg/day of L-glutamine (e.g g/kg/day alanyl-glutamine dipeptide

33 Recommendations: PN & EN gln Canadian, 2015 We recommend that high dose combined parenteral and enteral glutamine supplementation NOT be used in critically ill patients. There are insufficient data to make a recommendation on the use of enteral glutamine vs. parenteral dipeptide supplementation. However given concerns of glutamine supplementation, we strongly recommend that glutamine supplementation NOT be used in critically ill patients, hence we do not recommend the use of enteral glutamine or parenteral dipeptides.

34 Specialised AA Amino acids EAA Conditionally EAA Non EAA Citrulline

35 Citrulline Arg & gln citrulline arginine protein Intermediate of urea cycle Not incorporated into proteins? Regulate nitrogen homeostasis Other fx Oxidant scavenging Affects NO production levels: sepsis, ARDS Gunst J 2018

36 To supplement or not to supplement? Possible role Severe sepsis ARDS Problems Lack of info on application (clinical setup and EN/PN) Gunst 2018

37 Specialised AA Amino acids EAA Conditionally EAA Non EAA Taurine

38 Taurine Not incorporated into proteins Functions Osmoregulation Antioxidative Anti-inflammatory levels: critically ill Gunst J 2018

39 Taurine Enteral omega 3 fatty acid, alpha linolenic acid, and antioxidant supplementation in acute lung injury study (OMEGA study) in ventilator free days > days with organ failure mortaility Other immune enhancing components? Gunst J 2018

40 To supplement or not to supplement? Possible role Critical illness ALI Problems Lack of info on application Gunst 2018

41 Specialised AA Amino acids EAA Conditionally EAA Non EAA Arginine Glutamine Citrulline Taurine

42 What can we do? Arginine supplementation Trauma, surgery, chronic infections Glutamine supplementation (TPN) Critical illness Select an appropriate protein source Whey protein >>>> casein, soya High in BCAA (leucine) Higher in cysteine Methionine: Casein > whey > soya

43 Recommendations Timing, optimal dose, composition unclear Supplement responsible Choose good quality protein source with all AA Adequately powered RCT showing benefit in critical illness Not just physiological but also clinical outcomes

44 Thank You

45 References Malone A, Hamilton C. The Academy of nutrition and Dietetics / The American Society for parenteral and Enteral Nutrition Consensus malnutrition characteristics: Application in practice. Nutr Clin Prac 2013;28: Marshall K. (2004). Therapeutic Applications of Whey Protein. Alternative Medicine Review, Volume 9, Number 2: p Wolfe RR. The 2017 Sir David Cuthbertson lecture. Amino acids and muscle protein metabolism in critical care. Clin Nurt 2018;37: Pierre JF, Heneghan AF, Lawson CM, Wischmeyer PE, Kozar RA, Kudsk KA. Pharmaconutrition review: physiological mechanisms. J Paren Enter Nutr,2013;37(1):51S-65S

46 References Gunst J, Vanhorebreek I, Thiesssen SE, van den berghe G. Amino acid supplements in critically ill patients. Pharm Research 2018;130: McCarthy MS, Martindale RG. Immunonutrition in critical illness: What is the role? Nutr Clin Prac 2018;33(3): Ochoa Gautier JB, Martindale RG, Rugeles SJ, Hurt RT, Taylor B, Heyland DK, McClave SA. How much and what type of protein should a critically ill patient receive? Nutr Clin Prac 2017;32(1):6S- 14S Moore FA, Phillips SM, McClain CJ, Patel JJ, Martindale RG. Nutrition support for persistent inflammation, imuunosuppression, and catabolism syndrome. Nutr Clin Prac 2017;32(1):121S-127S

47 References Taylor BE, McClave SA, Martindale RG, Warren MM, Johnson DR, Braunschweig C et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Crit Care Med 2016;44(2): Stehle P, Ellger B, Kojik D, Feuersenger A, Schneid C, Stover J, Scheiner D, Westphal M. Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials. Clin Nutr 2017;17:75-85

48 References Canadian Clinical Practice Guidelines Committee Canadian Clinical Practice Guidelines. &id=14&itemid=14 [accessed: 14/01/2016) Kreyman KG et al. ESPEN Guidelines on Enteral Nutrition: Intensive care. Clin Nutr 2006;25: