Anti-Oxidants Can Modulate This Response

Immunonutrition

23/10/10

SP Notes

PY Mindmaps

OH

= feeding (enteral or TPN) enriched with various pharmaconutrients (arginine, glutamine, omega-3-fatty acids, nucleotides and anti-oxidants: copper, selenium, zinc, vitamins B, C and E)

CRITICAL ILLNESS

- oxidative stress and SIRS -> free radical formation -> activation of nuclear transcription kappa B -> increase TNF alpha, IL-2, IL-2 receptors -> amplification of inflammatory cascade

- anti-oxidants can modulate this response

- in SIRS vitamins and trace elements are taken from the circulating compartment into tissues and organs -> to increase protein synthesis and immune cell production

- relative deficit in circulating trace elements and water soluble vitamins -> deficit in circulating anti-oxidants.

GENERAL PRINCIPLES

- some data to suggest benefit (no clear answer in literature)

- overall role in ICU not yet established

- fits with the physiology of critical illness (SIRS -> increased uptake of pharmaconutrients into tissues, losses from other sources, dilution with resuscitation, insufficient intake)

- IV replacement better than EN

- all important rather than just one nutrient or vitamin (give together)

- risk of toxicities

GLUTAMINE

- many roles:

(1) oxidative fuel

(2) nucleotide precursor

(3) serves a role in signalling states of injury and illness

(4) tissue protection

(5) anti-inflammatory/immune regulation

(6) preservation of tissue metabolic function in stress states

(7) antioxidant

(8) antenuation of iNOS expression

- used by enterocytes, lymphocytes, neutrophils and macrophages

- essential in catabolic illness and vunerable to depletion

- in early trials has been shown to improve outcomes in the critically ill

- in burns patients (Garrel, 2003, CCM) RCT -> decreases bacteraemia, mortality and length of stay

- subsequent data in larger trials in unselected patients -> no such benefit

- difficult to put glutamine in TPN -> now more stable as dipeptides: data conflicting but there is a trend towards a mortality reduction.

SELENIUM

- crucial to regulation of glutathione peroxidase = major scavenging system for oxygen free radicals

- small trial: potential benefit if given in high dose

- recent large trial of IV selenium vs placebo (Angstwurm, 2007, CCM): statistically non-significant reduction in mortality

ARGININE

- precursor of NO, polyamides (important in lymphocyte aggregation) and nucleosides

- meta-analysis (Heyland, 2001, JAMA): reduction in hospital stay and infections, no change in mortality, maybe increased mortality in sepsis

ANTI-OXIDANT SUPPLEMENT TRIALS

- have focused on 5 micronutrients: copper, selenium, zinc, vitamins B, C and E

- recent meta-analysis:

-> positive influence on survival (RR 0.65)

-> parenteral antioxidants associated with significant reduction (RR 0.56)

-> no significant difference in enteral supplementation

-> selenium seem to be the most important

- cardiac and trauma RCT

- antioxidants (selenium, zinc, vitamin B1) vs placebo

-> shorter hospital stay

-> resolution of organ failure faster

- other RCTs (small)

- trace element supplementation (copper, selenium, zinc) vs placebo

-> reduction in nosocomial pneumonia

TOXICITIES

- all trace elements and vitamins have dose response curves

- zinc: >50mg/day -> immunosuppression, progressive cholestasis

- copper: liver damage

- selenium: >5mcg/kg/day

- vitamin E: chronic ingestion -> increased mortality

Jeremy Fernando (2011)