Pharmaconutrition: Selected Nutrients and Their Influence on Patient Outcomes
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Pharmaconutrition: Selected Nutrients and Their Influence on Patient Outcomes The Canadian Clinical Practice Guidelines. Daren K. Heyland, MD, FRCPC, MSc. Queen’s University, Kingston, Ontario. Updated July 2006 . www.criticalcarenutrition.com. Immunonutrition: Cocktail Approach?.

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Pharmaconutrition: Selected Nutrients and Their Influence on Patient OutcomesThe Canadian Clinical Practice Guidelines

Daren K. Heyland, MD, FRCPC, MSc

Queen’s University, Kingston, Ontario


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Updated July 2006 Patient Outcomes

www.criticalcarenutrition.com


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Immunonutrition: Patient Outcomes Cocktail Approach?

  • Specific nutrients found to have effects on immune system, metabolism, and GI structure and function

    • Arginine

    • Glutamine

    • Omega-3 fatty acids

    • Nucleic acids

    • others

  • Individual effect on clinical outcomes?


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endothelial dysfunction Patient Outcomes

activation of coagulation/complement

Insult

  • infection

  • trauma

  • I/R

  • hypoxemic/

  • hypotensive

Activation of

PMN’s

elaboration of cytokines,

NO, and other mediators

generation of OFR

(ROS + RNOS)

Role of

GIT

mitochondrial dysfunction

oxidative stress

=

cellular = energetic

failure

Death

organ = failure

Pathophysiology of Critical Illness

Key nutrient deficiencies

(e.g. glutamine, selenium)

Arginine


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Elective Surgical Patient Patient Outcomes

  • cellular immune dysfunction

    • T-cell

  • decrease cytokine activation

    • IL-2, IFN


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Elective Surgical Patient Patient Outcomes

arginase

arginine

expression of zeta chain

Taheri Clin Cancer Res 2001 ;7:958


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= Patient Outcomes


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1.18 (0.88,1.58) Patient Outcomes


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Which Nutrients? Patient Outcomes

Which Patients?

Population

Nutrients

Canadian Clinical Practice Guidelines JPEN 2003;27:355

www.criticalcarenutrition.com


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Underlying Rationale for Framework Patient Outcomes

  • No scientific rationale for combining nutrients together; need to consider them alone

  • Empirical evidence that the nutrients have different treatment effects across populations


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Which Nutrient for Which Population? Patient Outcomes

Population

Nutrients

Canadian Clinical Practice Guidelines JPEN 2003;27:355



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Underlying Pathophysiology Patient OutcomesRole of Nitric Oxide

Mitaka Shock 2003;19: 305


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Optimal NO-Balance Patient Outcomes

cNOS

- Microcirculation- Immune augmentation 

Benefitial

Effect of Arginine induced NO formation

Arginine / NO availability

Harmful

cNOS + iNOS

- Hemodynamic instability- Immune Suppression- Cytotoxicity- Organe dysfunction

Suchner Brit J Nutrition 2001


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Effect of Arginine-supplemented diets on Mortality Patient Outcomes

www.criticalcarenutrition.com


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Effect of Arginine-supplemented diets on Infectious complications

www.criticalcarenutrition.com


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Effect of Arginine-supplemented diets in Critically Ill Patients

  • Possible mortality in septic pts. Crit Care Med 1995;23:436

    Dent, Crit Care Med 2003

    Bertolini Int Care Med 2003;29:834

  •  cost.

  • Lack of treatment effect.

But what about ...



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Potential Beneficial Effects of Glutamine Patients

Enhanced Heat

Shock Protein

GLN

Pool

Enhanced

insulin

sensitivity

Decreased Free

Radical availability

(Anti-inflammatory action)

NF-B

?

Inflammatory Cytokine

Attenuation

Glutathione

Synthesis

Glutamine

Therapy

Reduced

Translocation

Enteric Bacteria

or Endotoxins

Maintenance of

Intestinal

Mucosal Barrier

Fuel for

Enterocytes

Critical Illness

Nuclotide

Synthesis

Preservation

of TCA Function

Reduction of

Infectious complications

Maintenance of

Lymphocyte

Function

Fuel for

Lymphocytes

Anti-catabolic

effect

Preserved

Cellular

Energetics-

ATP content

Preservation of

Muscle mass

GLN

pool


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Effect of Glutamine: Patients

A Systematic Review of the Literature

Infectious Complications

www.criticalcarenutrition.com


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Effect of Glutamine: Patients

A Systematic Review of the Literature

Mortality

www.criticalcarenutrition.com


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Results of subgroup analysis Patients

EN vs PN?




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Mechanisms of Action Patients

  • Mediator formation depends on the phospholipid fatty acid content of arachidonic acid (AA) in inflammatory cell membranes

  • It is possible to modulate the content of AA in inflammatory cell membranes by changing lipid composition of the diet


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Mechanisms of Action Patients

GLA

EPA

Arachidonic Acid

Borage Oil

Fish Oil

CyclooxygenaseLipoxygenase

DGLA

Substitution of AA

By EPA

Resulting in:

Substitution of AA

By DGLA

resulting in:

Decrease in

Pro-Inflammatory

Eicosanoids

(LTB4, TXA2, PGE2)

Less Inflammatory

Eicosanoids

(TXA3, PGE3, LTB5)

PGE1 and Less

Inflammatory

Eicosanoids


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Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI

  • RCT of 146 critically ill patients with ALI and BAL+ for WBCs

  • Double-blinded; ITT

  • Experimental: Oxepa®

  • Control: high fat diet

  • Groups well matched at baseline

P=0.02

P=0.03

P=0.17

Gadek Crit Care Med 1999;27:1409


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Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI

  • RCT of 100 critically ill patients with ALI

  • Single center

  • unblinded; not ITT

  • Experimental: Oxepa®

  • Control: high fat diet

  • Oxepa associated with improved oxygenation and lung compliance

Singer Crit Care Med 2006:34;1033


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Effect of Fish Oils/Borage Oils and antioxidants in Critically Ill with ALI

  • RCT of 165 critically ill patients with ARDS secondary to sepsis

  • Double-blinded; not ITT

  • Experimental: Oxepa®

  • Control: high fat diet

  • Oxepa associated with:

    • improved oxygenation

    • More Vent free days

    • More ICU free days

    • Fewer new organ failures

P=0.04

Pontes -Arruda Crit Care Med 2006:34;2345


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Overall Effect on Mortality Critically Ill with ALI

www.criticalcarenutrition.com


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Interpretation of Studies? Critically Ill with ALI

  • treatment effect of antioxidants?

  • treatment effect of borage oils?

  • comparison to standard enteral feeding products?

How do you interpret

the findings?



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Rationale for Antioxidants Critically Ill with ALI

Infection

InflammationIschemia

OFR

CONSUMPTION

OFR

PRODUCTION

Depletion of

Antioxidant Enzymes

OFR Scavengers

Vitamins/Cofactors

Impaired

- organ function

- immune function

- mucosal barrier function

OXIDATIVE

STRESS

OFR production > OFR consumption =

Complications and Death


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Rationale for Antioxidants Critically Ill with ALI

  • Endogenous antioxidant defense mechanisms

    • Enzymes (superoxide dismutase, catalase, glutathione perioxidase, glutathione reductase including their cofactors Zn and Selenium)

    • Sulfhydryl group donors (glutathione)

    • Vitamins E, C, and B-carotene


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Rationale for Antioxidants Critically Ill with ALI



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Which Nutrient for Which Population? Ill

Population

Nutrients

Canadian Clinical Practice Guidelines JPEN 2003;27:355


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RE Illducing Deaths from OXidative Stress:The REDOXS study

antioxidants

Factorial 2x2 design

glutamine

R

Concealed

Stratified by

1200 ICU patients

R

placebo

Evidence of

  • site

organ failure

antioxidants

  • Shock

R

placebo

placebo


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Critical Care Nutrition Web Site Ill

www.criticalcarenutrition.com

  • web based clinical practice guidelines

  • summaries of evidence

  • online survey of current practice

  • benchmarking (other sites and the clinical practice guidelines)

  • tools (protocols, etc)

  • research related news