Oxidative stress occurs when there is an imbalance between production of reactive oxygen species and a body's antioxidant defenses. Selenium is an important antioxidant that helps regulate oxidative stress through selenoproteins like glutathione peroxidase. Studies have shown that critically ill patients often have low selenium levels associated with higher illness severity and mortality. Giving selenium supplements to ICU patients increased their selenium and glutathione peroxidase levels and improved clinical outcomes, though larger studies are still needed to determine if selenium reduces mortality.
2. • What is Oxidative stress
• Why is Oxidative Stress important
• How does Selenium fit into Oxidative stress
• Selenium (Se) in critical illness
• What’s the current evidence for Se in ICU
3. • Oxidant production is normally balanced by
antioxidant systems (Reduction by enzyme
scavengers and dietary antioxidants)
• Redox imbalance is caused by excessive
production of ROS / NOS or decrease in
antioxidants + destruction of enzyme
scavengers.
• When ROS > Reductive capacity there is
OXIDATIVE STRESS
4.
5.
6. • Selenium is a trace mineral found in minute
quantities in the body
• RDA 60ug /day
• Serum Se level for optimal Selenoprotein
function is around 100ug/L
• In Serum 40% GSH-Px / 10% Albumin / 50%
Selenoprotein-P
• Found in Bread, cereals, fish, meat
7. • Plasma Se levels fall in critical illness
• 1998 Forceville et al showed low plasma
selenium at ICU admission correlated with
mortality
• Se level inversely correlated with APACHE 2
• Se level inversely correlated with Sepsis
Severity
Critcal Care Medicine 1998;26:1536-44
10. • Why exactly is the Se level low in SIRS
– Change in Albumin concentration
– Changes in distribution of Selenoprotein-P
– Consumed in REDOX
– Haemo-diluton
– Reduced Nutritional intake
11. • 1999 Angstwurm etal demonstrated
increased plasma Se levels and GSH-Px after
replacing Se
• Activity of the Se-dependent enzyme GSH-Px
parallels serum Se with increasing activity
after replacement.
• Similar results in small studies with Trauma
Critical care medicine 1999;27:1807-13
20. • Se is essential trace element for maintaining
balance in Oxidation- Reduction
• Reactive Oxygen and Nitrogen species can
damage cells
• No clear evidence that large doses of Se avoid
the reduce mortality
Notes de l'éditeur
Pathogens activate the immune system which causes a burst in Oxidation and an excess of H2O2 and HOCl. Inside the cell the H2O2 acts to stimulate NF-kB also activated by cytokines and Met-Hb. This stimulates inducible nitricoxide synthase (iNOS) thus producing NO which provokes inhibition of the electron transfer chain (ECT). This results in the production of SuperOxide (ONOO) which then decomposes to the highly reactive species OH and NO2….. which then damage the mitochondria and together with the inhibition of the ECT cause a fall in the production of ATP. In the Cytosyl increased activities of three enzymes (NADPH Oxidase / Cox2 / Xanthine Oxidase XO) produces superoxide ONOO which via DNA damage poly (ADP-ribose) polymerase (PARP) activation and consumption of NAD+ impairing the ETC. Superoxide is dismutased in the mitochondria by Manganeese superoxide dismutase (MnSOD) to H2O2 which closes the positive feedback loop. Over producyion of intracellular NO leads to leakage into the plasma which lyses RBCand HOCL causes pore formation in the RBC membranes t.hus freeing Met-Hb which increases Fe availability for pathogen proliferation. Met-Hb provokes the activation of NF-kB closing the NO generating loop
GSH is the reduced monomeric Glutathione GS-SG represents Glutathione Disulphide This is a Multiple step reaction involving selnocysteine. Selenoproteins are proteins that contain a Se-cysteine residue (Se-Cys) Important to remember that GSH supplementation has not been found to be helpful???
134 consecutive admissions with sepsis / SIRS
Single centre Randomised controlled open label pilot study. 42 Patients with SIRS and minimum APACHE 2 of 15 Se replaced in decreasing amounts starting with 500ug
Se levels normalised within 3 days in the Rx group GSH-Px levels also normalised within 3 days in the RX group
Randomised controlled factorial designed trial 500 patients needing ICU/HDU greater than 24hrs and needing PN Either 20.2g glutamine or 500ug Se or both
Apache 2 score 20 27% were under nourished
No Reduction in Infections with either Glutamine or Se Multiple sub-group analyis with small groups Controversy with dose and duration of treatment