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Roger Harris on Oxidative Stress

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Roger Harris, the Bedside Critical Care big dog gives his last talk of the 2012 conference. From the maker of Sex and Nutrition comes Oxidative Stress. Roger specifically discusses:
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

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Roger Harris on Oxidative Stress

  1. 1. • 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
  2. 2. • Oxidant production is normally balanced byantioxidant systems (Reduction by enzymescavengers and dietary antioxidants)• Redox imbalance is caused by excessiveproduction of ROS / NOS or decrease inantioxidants + destruction of enzymescavengers.• When ROS > Reductive capacity there isOXIDATIVE STRESS
  3. 3. • Selenium is a trace mineral found in minutequantities in the body• RDA 60ug /day• Serum Se level for optimal Selenoproteinfunction is around 100ug/L• In Serum 40% GSH-Px / 10% Albumin / 50%Selenoprotein-P• Found in Bread, cereals, fish, meat
  4. 4. • Plasma Se levels fall in critical illness• 1998 Forceville et al showed low plasmaselenium at ICU admission correlated withmortality• Se level inversely correlated with APACHE 2• Se level inversely correlated with SepsisSeverityCritcal Care Medicine 1998;26:1536-44
  5. 5. © Williams & Wilkins 1998. All Rights Reserved. Published by Lippincott Williams & Wilkins, Inc. 3Figure 1Selenium, systemic immune response syndrome, sepsis,and outcome in critically ill patients.Forceville, Xavier; Vitoux, Dominique; Gauzit, Remy;Combes, Alain; Lahilaire, Pierre; Chappuis, PhilippeCritical Care Medicine. 26(9):1536-1544, September1998.Figure 1 . Admission plasma selenium concentrationrelated to Acute Physiology and Chronic HealthEvaluation (APACHE) II severity score. Dashed line, mean+/- SD normal plasma selenium value (1.00 +/- 0.15[micro sign]mol/L). r2 = .11; p < .0001.
  6. 6. © Williams & Wilkins 1998. All Rights Reserved. Published by Lippincott Williams & Wilkins, Inc. 5Figure 2Selenium, systemic immune response syndrome, sepsis,and outcome in critically ill patients.Forceville, Xavier; Vitoux, Dominique; Gauzit, Remy;Combes, Alain; Lahilaire, Pierre; Chappuis, PhilippeCritical Care Medicine. 26(9):1536-1544, September1998.Figure 2 . Admission plasma selenium concentrationrelated to severity of sepsis. p <or=to .05 for sepsis vs.severe sepsis; p <or=to .05 for sepsis vs. septic shock(analysis of variance). Dashed line, mean +/- SD normalplasma selenium concentration (1.00 +/- 0.15 [microsign]mol/L); n, number of patients, including, inparentheses, number of nonsurviving patients, for eachsepsis severity grade. Values are expressed as median(middle line in the box) with the top and bottom of thebox encompassing the 25th to the 75th percentiles;capped lines indicate the tenth to 90th percentiles of thedata; circles, values above the 90th and below the tenthpercentiles.
  7. 7. • 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
  8. 8. • 1999 Angstwurm etal demonstratedincreased plasma Se levels and GSH-Px afterreplacing Se• Activity of the Se-dependent enzyme GSH-Pxparallels serum Se with increasing activityafter replacement.• Similar results in small studies with TraumaCritical care medicine 1999;27:1807-13
  9. 9. © 1999 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2Figure 1Selenium replacement in patients with severe systemicinflammatory response syndrome improves clinicaloutcome.Angstwurm, Matthias; Schottdorf, Juergen; Schopohl,Jochen; Gaertner, RolandCritical Care Medicine. 27(9):1807-1813, September1999.Figure 1 . Serum selenium concentrations ([mu]g/L) inpatients in the Se- (control) group and the Se+ (selenium-treated) group at days 0, 3, 7, and 14. Se+ vs. Se-: day 0, p> .05; day 3, p p p = .003. Bold lines represent themedian, boxes represent 75th and 25th percentiles, thesmall lines at the top and bottom of each box indicate the95th and 5th percentiles of the distribution. Dotted linesrepresent the normal range (70-120 [mu]g/L, 0.88-1.52[mu]mol/L).
  10. 10. © 1999 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 3Figure 2Selenium replacement in patients with severe systemicinflammatory response syndrome improves clinicaloutcome.Angstwurm, Matthias; Schottdorf, Juergen; Schopohl,Jochen; Gaertner, RolandCritical Care Medicine. 27(9):1807-1813, September1999.Figure 2 . Serum glutathione peroxidase activities (U/L) inpatients in the Se- (control) group and the Se+ (selenium-treated) group at days 0, 3, 7, and 14. Se+ vs. Se-: day 0, p> .05; day 3, p p p = .013. Bold lines represent themedian, boxes represent the 75th and 25th percentiles,the small lines at the top and bottom of each box indicatethe 95th and 5th percentiles of the distribution. Dottedlines represent the normal range (>96 U/L).
  11. 11. • Se is essential trace element for maintainingbalance in Oxidation- Reduction• Reactive Oxygen and Nitrogen species candamage cells• No clear evidence that large doses of Se avoidthe reduce mortality

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