Post on 07-May-2015
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You Are What You Eat!
David Bihari Intensive Care Physician
Prince of Wales Hospital and Lismore Base Hospital
Conflicts of Interest
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”!
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!
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
Crick and Watson 1952
The Mediterranean Diet
1975
The Cambridge “Beer and Crisps” Diet
Nutrition and exercise
Fat Men
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
Splanchnic Blood Flow
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”
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
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)
Some Cult Leaders
The Golden Calf Phenomenon
Learning from the Past
Criminal terrorist or political prisoner?
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
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
TreaGng MalnutriGon Learning from the Past
The Refeeding Syndrome – death from hypophosphataemia (plus hypomagnesaemia)
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
Conflicts of Interest
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
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
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
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
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%
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
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)
cNOS
cNOS + iNOS
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Arginine / NO availability
Optimal NO-Balance
- Hemodynamic instability - Immune Suppression - Cytotoxicity - Organ dysfunction
- Microcirculation ↑ - Immune augmentation ↑
Suchner Brit J Nutrition 2001
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
A Convert to Heylandism
• The paGent must be fed early
• The paGent must go on TPN
• The paGent must receive glutamine
• The “Maya” factor!
• A Killer Penis in Minutes – www.libidus-‐pill.com
• Penis Enlargement Chart – www.Penis-‐Enlargement-‐Chart.com
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