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You Are What You Eat! David Bihari Intensive Care Physician Prince of Wales Hospital and Lismore Base Hospital

Bihari: You are what you eat

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David Bihari is an Intensivist from Prince of Wales Hospital in Sydney. He is particularly interested and passionate about nutrition in the critically ill, and has been involved in research in this area for many years. Here he talks about how we feed in ICU.

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You  Are  What  You  Eat!  

David  Bihari  Intensive  Care  Physician  

Prince  of  Wales  Hospital  and  Lismore  Base  Hospital  

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Conflicts  of  Interest  

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Conflicts  of  Interest  

•  “TPN  Czar”  of  Prince  of  Wales  Hospital  •  Medical  representaGve  on  the  TPN  Forum  

•  In  a  previous  life,  performed  and  published  research  in  the  area  of  “immunonutriGon”  

•  Tendency  to  believe  in  “one’s  own  bull  shit”!    

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You  Are  What  You  Eat  

•  The  noGon  that  to  be  fit  and  healthy  you  need  to  eat  GOOD  FOOD!  

•  “Dis  moi  ce  que  tu  manges,  je  te  dirai  ce  que  tu  es”  Anthelme  Brillat-­‐Savarin  1826  

•  1942  Lindahr  –  You  are  what  you  eat:  how  to  win  and  keep  healthy  with  diet  

•  More  Catholic  than  catabolic?  – TransubstanGaGon!  

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Things  Your  Mother  Taught  You  

•  Eat  your  greens  ….not  too  many  Mars  bars  …because  you  are  what  you  eat!  –  Avoid  the  “Cambridge  diet”  of  beer  and  crisps  

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Crick and Watson 1952

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The  Mediterranean  Diet  

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1975

The  Cambridge  “Beer  and  Crisps”  Diet    

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Nutrition and exercise

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Fat  Men  

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Things  Your  Mother  Taught  You  

•  Eat  your  greens  ….not  too  many  Mars  bars  …because  you  are  what  you  eat!  – Avoid  the  “Cambridge  diet”  of  beer  and  crisps  

•  Don’t  go  swimming  on  a  full  stomach!  –   Nutrients  in  the  lumen  of  the  bowel  promote  splanchnic  blood  flow  

– “Trophic  enteral  feeding”  :  10  –  30  mL/hour  

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Splanchnic  Blood  Flow  

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1909 - British lady “suffragette” (fighting for the rights of women) put in prison and on hunger strike

The Intensivist? “more intensive than caring”

The Dietician? “obsessing about calories”

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NutriGonal  Support  2014  

•  Energy  intake  may  not  be  so  important  – Hypocaloric  enteral  feeding  is  widespread  – Trophic  feeding    

•  ResurrecGon  of  TPN  through  meta-­‐analysis  (2005)  since  its  crucifixion  by  meta-­‐analysis  (1998)  

•  IntroducGon  of  glutamine  containing  TPN  by  meta-­‐analysis  

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NutriGonal  Support  2014  

•  Crucifixion  of  TPN  –  EPaNIC  study  – Not  enough  protein!  

•  Crucifixion  of  glutamine  –  the  REDOX  study    – Too  much  nitrogen  given  to  paGents  too  sick  to  uGlise  

– Not  enough  nutriGon!  •  New  intravenous  lipid  soluGons  available    •  Crucifixion  of  enteral  immune  modulaGng  nutriGon  (specifically  arginine  containing  feeds  eg.  “Impact”)  by  meta-­‐analysis  (2003)  

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Some  Cult  Leaders  

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The Golden Calf Phenomenon

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Learning  from  the  Past  

Criminal terrorist or political prisoner?

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Lessons  from  Northern  Ireland  “Hunger”  

Bobby Sands 61 days Francis Hughes 59 days Raymond McCreesh 61 days Patsy O’Hara 61 days Joseph McDonnell 61 days Martin Hurson 44 days Kevin Lynch 71 days Kieran Doherty 73 days Thomas McElwee 62 days Micky Devine 61 days

Cause of death - infection

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StarvaGon  in  hospital  is  unacceptable  

•  Nutrients  -­‐  unlike  drugs  -­‐  are  required  for  the  maintenance  of  good  health,  survival  

•  10  IRA  hunger  strikers  fasted  to  death  over  a  mean  of  62  +  3  days  –  Died  from  infecGon  

•  Australian  medical  student  lost  in  Nepal  lived  for  42  days  eaGng  only  snow  (Ann  Int  Med  1997)  :  lost  19  kg,    80  to  61  kg  

•  StarvaGon  is  not  the  same  as  criGcal  illness  •  Malnourished  paGents  form  a  special  group  –  Li-le  /me  to  waste  before  ins/tu/ng  support      

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TreaGng  MalnutriGon  Learning  from  the  Past  

The Refeeding Syndrome – death from hypophosphataemia (plus hypomagnesaemia)

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The  Refeeding  Syndrome  •  First  described  in  Far  East  Japanese  

prisoners  amer  2nd  World  War  •  Schnitker  et  al  Ann  Inter  Med  1951  

•  StarGng  to  eat  associated  with  development  of  cardiac  failure  –  DepleGon  of  intracellular  PO4,  Mg  &  K  

•  Decreased  secreGon  of  insulin  –  Refeeding  with  CHO  results  in  increased  

insulin  secreGon,  cellular  uptake  of  PO4,  Mg  and  K  •  First  4  days  of  refeeding  •  Arrhythmias,  sudden  death,  heart  failure,  rhabdomyolysis,  seizures  

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Conflicts  of  Interest  

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The  REDOX  Study  –  4  arms  

" 0.35  Gm/kg/day  iv  glutamine  plus  30  Gm  enteral  glutamine    " 0.5  Gm/kg/day  of  iv  dipepGde  alanyl-­‐glyutamine  " 42.5  Gm  of  enteral  alanyl-­‐glutamine  and  glycine-­‐glutamine  

•  AnGoxidants    –  500  mcg  selenium  iv,  300  mcg  enterally  –  20  mg  zinc,  10  mg  beta-­‐carotene  enterally  –  500  mg  vitamin  E,  1500  mg  vitamin  C  enterally  

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Arginine  as  an  Immunonutrient  

•  Arginine  (C6H14N4O2,  mw  174.20)  – EssenGal  amino  acid  during  childhood  – CondiGonally  essenGal  in  adults  –  Incorporated  into  protein  at  4.7%  per  mole  – Found  in  meat,  fish,  dairy  products,  brown  rice,  nuts,  raisons,  whole  wheat  

– Glutamine,  glutamate  and  citrulline  are  also  dietry  sources  of  arginine  •  IntesGnal  conversion  to  citrulline  •  Renal  and  hepaGc  conversion  to  arginine  

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Watermelon  ConsumpGon  and  Plasma  Arginine  Levels    

•  Collins  et  al  NutriGon  2007;  23:  261-­‐266  •  Watermelon  is  a  rich  source  of  citrulline  •  Controlled  diet  plus  0  /  780  g  /  1560  g  of  watermelon  juice  – Equivalent  to  1  g  and  2  g  citrulline  /  day  

•  Amer  3  weeks,  fasGng  plasma  arginine  levels  increased  by  12  and  22%  respecGvely  

•  No  change  in  citrulline  levels  •  18%  increase  in  ornithine  levels  

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Arginine  as  an  Immunonutrient  

•  Number  of  supposed  beneficial  effects  – Anabolic  secretagogue  sGmulaGng  the  secreGon  of  growth  hormone,  glucagon,  insulin  and  IGF-­‐1  

– UGlized  in  the  synthesis  of  creaGne  in  skeletal  muscle    •  Important  for  high  energy  creaGne  phosphate  

– Enhances  wound  healing  – Enhances  cell  mediated  immunity  in  elecGve  surgical  paGents  

– Substrate  for  the  formaGon  of  NO  

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Metabolism of L-arginine by nitric oxide synthase (NOS) and arginase Nitric oxide synthase oxidatively degrades L-arginine into L-citrulline and nitric oxide (NO), whereas arginase hydrolyses L-arginine to urea and L-ornithine

<5%

>95%

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Arginine  in  Sepsis  •  Role  of  nitric  oxide  (NO)  in  sepsis    – Key  mediator  of  the  vasodilataGon  •  Appropriate  release  maintains  microvascular  blood  flow  •  Excessive  release  associated  with  hypotension  

– Key  mediator  in  macrophages  and  white  cells  for  killing  of  invading  microorganisms  •  Excessive  release  associated  with  Gssue  injury?  

–  Splanchnic  mucosal  injury  – Myocardial  dysfuncGon  –  Skeletal  muscle  mitochondrial  dysfuncGon  

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Arginine  in  Sepsis  

•  The  Heyland  Hypothesis  – Arginine  in  sepsis  may  be  contra-­‐indicated  since  it  may  enhance  the  producGon  of  NO  and  worsen  any  associated  Gssue  injury  

– Signal  of  detrimental  effect  obtained  from  studies  of  arginine  containing  enteral  nutriGon  

–  Ignores  the  evidence  of  the  detrimental  effects  of  blocking  the  synthesis  of  NO  in  sepGc  shock  using  N-­‐methyl-­‐L-­‐arginine  (546C88)  

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cNOS

cNOS + iNOS

Effe

ct o

f Arg

inin

e in

duce

d N

O fo

rmat

ion

Har

mfu

l B

enef

itial

Arginine / NO availability

Optimal NO-Balance

- Hemodynamic instability - Immune Suppression - Cytotoxicity - Organ dysfunction

- Microcirculation ↑ - Immune augmentation ↑

Suchner Brit J Nutrition 2001

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2/22 = 9% 3/31 = 10% 0/37 = 0% 3/98 = 3%

36/296 = 12% 2/33 = 6%

28/170 = 16% 12/36 = 33%

2/43 = 5% 3/30 = 10% 6/29 = 21%

180/390 = 46% 45/176 = 26%

Heyland DK et al. Should Immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001; 286: 944-953

1391 “critically ill” patients studied with 322 deaths (23%)

13 studies included

Relative risk 1.18; 95%CI 0.88-1.58

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A  Convert  to  Heylandism  

•  The  paGent  must  be  fed  early  

•  The  paGent  must  go  on  TPN  

•  The  paGent  must  receive  glutamine  

•  The  “Maya”  factor!  

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•  A  Killer  Penis  in  Minutes  –  www.libidus-­‐pill.com  

•  Penis  Enlargement  Chart  –  www.Penis-­‐Enlargement-­‐Chart.com  

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