Antioxidant supplementation in sepsis and systemic inflammatory response syndrome

Objective:Summarize the current knowledge about oxidative stress-related organ dysfunction in inflammatory and septic conditions, and its potential prevention and treatment by antioxidants in critically ill patients, focusing on naturally occurring antioxidants and clinical trials. Study Selection:PubMed, MEDLINE, and personal database search. Synthesis:Plasma concentrations of antioxidant micronutrients are depressed during critical illness and especially during sepsis. The causes of these low levels include losses with biological fluids, low intakes, dilution by resuscitation fluids, as well as systemic inflammatory response syndrome-mediated redistribution of micronutrients from plasma to tissues. Numerous clinical trials have been conducted, many of which have shown beneficial effects of supplementation. Interestingly, among the candidates, glutamine, glutathione, and selenium are linked with the potent glutathione peroxidase enzyme family at some stage of their synthesis and metabolism. Conclusions:Three antioxidant nutrients have demonstrated clinical benefits and reached level A evidence: a) selenium improves clinical outcome (infections, organ failure); b) glutamine reduces infectious complication in large-sized trials; and c) the association of eicosapentaenoic acid and micronutrients has significant anti-inflammatory effects. Other antioxidants are still on the clinical benchmark level, awaiting well-designed clinical trials.

[1]  A. Nathens,et al.  Randomized, Prospective Trial of Antioxidant Supplementation in Critically Ill Surgical Patients , 2002, Annals of surgery.

[2]  Michael A Dubick,et al.  HIGH-DOSE VITAMIN C INFUSION REDUCES FLUID REQUIREMENTS IN THE RESUSCITATION OF BURN-INJURED SHEEP , 2005, Shock.

[3]  P. Calder.  Use of fish oil in parenteral nutrition: rationale and reality , 2006, Proceedings of the Nutrition Society.

[4]  M. Berger.  Can oxidative damage be treated nutritionally? , 2005, Clinical nutrition.

[5]  A. Combes,et al.  Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. , 1998, Critical care medicine.

[6]  E. Roth,et al.  Assessing the antioxidative status in critically ill patients , 2004, Current opinion in clinical nutrition and metabolic care.

[7]  H. Matsuda,et al.  Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. , 2000, Archives of surgery.

[8]  A. Day,et al.  Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study. , 2007, JPEN. Journal of parenteral and enteral nutrition.

[9]  P. Stehle,et al.  Parenteral l-alanyl-l-glutamine improves 6-month outcome in critically ill patients* , 2002, Critical care medicine.

[10]  J. Vincent,et al.  Enteral feeding with a solution enriched with antioxidant vitamins A, C, and E enhances the resistance to oxidative stress , 2000, Critical care medicine.

[11]  K. Brown,et al.  Assessment of the trace element status of individuals and populations: the example of zinc and copper. , 2003, The Journal of nutrition.

[12]  C. Kretz-remy,et al.  Selenium: a key element that controls NF-kappa B activation and I kappa B alpha half life. , 2001, BioFactors.

[13]  R. Reiter,et al.  Significance of Melatonin in Antioxidative Defense System: Reactions and Products , 2000, Neurosignals.

[14]  P. Déchelotte,et al.  L-alanyl-L-glutamine dipeptide–supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: The French controlled, randomized, double-blind, multicenter study* , 2006, Critical care medicine.

[15]  L. Liu,et al.  Oxidative stress and metallothionein expression in the liver of rats with severe thermal injury. , 2002, Burns : journal of the International Society for Burn Injuries.

[16]  A. Baue.  MOF, MODS, and SIRS: what is in a name or an acronym? , 2006, Shock.

[17]  M. Oshiro,et al.  Alterations of serum selenium concentrations in the acute phase of pathological conditions. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[18]  James S. Wright,et al.  Prooxidant and antioxidant activity of vitamin E analogues and troglitazone. , 2005, Chemical research in toxicology.

[19]  A. D. de Gaudio,et al.  The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock. , 2000, American journal of respiratory and critical care medicine.

[20]  M. Zhang,et al.  Comparative observation of the changes in serum lipid peroxides influenced by the supplementation of vitamin E in burn patients and healthy controls. , 1992, Burns : journal of the International Society for Burn Injuries.

[21]  E. Bulger,et al.  An Argument for Vitamin E Supplementation in the Management of Systemic Inflammatory Response Syndrome , 2003, Shock.

[22]  W. Seeger,et al.  Serum alpha-tocopherol levels after high-dose enteral vitamin E administration in patients with acute respiratory failure , 2004, Intensive Care Medicine.

[23]  S. Sakaguchi,et al.  Oxidative stress and septic shock: metabolic aspects of oxygen-derived free radicals generated in the liver during endotoxemia. , 2006, FEMS immunology and medical microbiology.

[24]  A. Day,et al.  Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials , 2006, Critical care.

[25]  R. Nijveldt,et al.  Glutamine-enriched enteral feeding in trauma patients: reduced infectious morbidity is not related to changes in endocrine and metabolic responses. , 1999, JPEN. Journal of parenteral and enteral nutrition.

[26]  R. Merrell,et al.  Acute renal failure, oxalosis, and vitamin C supplementation: a case report and review of the literature. , 2000, Chest.

[27]  A. Shenkin,et al.  Markers of oxidative damage, antioxidant status and clinical outcome in critically ill patients , 2005, Annals of clinical biochemistry.

[28]  R. Ivatury,et al.  Antioxidant Therapy in the Prevention of Organ Dysfunction Syndrome and Infectious Complications after Trauma: Early Results of a Prospective Randomized Study , 1999, The American surgeon.

[29]  H. Delves.  Effect of inflammatory response on trace element and vitamin status. , 2001, Annals of clinical biochemistry.

[30]  P. Brätter,et al.  Influence of high dietary selenium intake on the thyroid hormone level in human serum. , 1996, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[31]  M. Rayman,et al.  The importance of selenium to human health , 2000, The Lancet.

[32]  L. Klotz,et al.  Glutathione Peroxidase Protects against Peroxynitrite-mediated Oxidations , 1997, The Journal of Biological Chemistry.

[33]  M. Berger,et al.  Selenium in intensive care: probably not a magic bullet but an important adjuvant therapy. , 2007, Critical care medicine.

[34]  Arthur S Slutsky,et al.  The role of oxidative stress in adult critical care , 2006, Free Radical Biology and Medicine.

[35]  R. Burk,et al.  Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. , 2005, Annual review of nutrition.

[36]  J. Wernerman,et al.  Modulation of endogenous glutathione availability. , 1999, Current opinion in clinical nutrition and metabolic care.

[37]  J. Pierce,et al.  Oxidative stress in critically ill patients. , 2002, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[38]  Sang Hyun Kim,et al.  Selenium Attenuates Lipopolysaccharide-Induced Oxidative Stress Responses Through Modulation of p38 MAPK and NF-κB Signaling Pathways , 2004, Experimental biology and medicine.

[39]  M. Berger,et al.  Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient , 2005, Intensive Care Medicine.

[40]  R. Black,et al.  Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial , 2004, The Lancet.

[41]  P. Wischmeyer.  Glutamine and heat shock protein expression. , 2002, Nutrition.

[42]  J. Schüttler,et al.  Selenium in Intensive Care (SIC): Results of a prospective randomized, placebo‐controlled, multiple‐center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock* , 2007, Critical care medicine.

[43]  M. Davies,et al.  Xanthine oxidase activity and free radical generation in patients with sepsis syndrome. , 1996, Critical care medicine.

[44]  J. Schopohl,et al.  Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. , 1999, Critical care medicine.

[45]  R. Koch,et al.  Omega-3 fatty acids improve the diagnosis-related clinical outcome* , 2006, Critical care medicine.

[46]  A. Sica,et al.  Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense. , 2002, The Journal of infectious diseases.

[47]  C. Kretz-remy,et al.  Selenium: A key element that controls NF-κB activation and IκBα half life , 2001 .

[48]  F. Spertini,et al.  Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. , 1998, The American journal of clinical nutrition.

[49]  Sun-Mee Lee,et al.  Effect of Alpha-Tocopherol on the Expression of Hepatic Vascular Stress Genes in Response to Sepsis , 2005, Journal of toxicology and environmental health. Part A.

[50]  C. Schorah.  Blood vitamin concentrations during the acute-phase response. , 1993, Critical care medicine.

[51]  M. Beck.  Selenium and host defence towards viruses , 1999, Proceedings of the Nutrition Society.

[52]  M. Berger,et al.  Update on clinical micronutrient supplementation studies in the critically ill , 2006, Current opinion in clinical nutrition and metabolic care.

[53]  S. Mallal,et al.  Assessment of precision and concordance of quantitative mitochondrial DNA assays: a collaborative international quality assurance study. , 2003, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[54]  E. Roth,et al.  Supply of R-α-lipoic acid and glutamine to casein-fed mice influences the number of B lymphocytes and tissue glutathione levels during endotoxemia , 2006, Wiener klinische Wochenschrift.

[55]  M. Berger,et al.  Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. , 2007, Clinical nutrition.

[56]  C. McClain,et al.  Effects of endotoxin on zinc metabolism in human volunteers. , 1997, The American journal of physiology.

[57]  A. Pontes-Arruda,et al.  Effects of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock* , 2006, Critical care medicine.

[58]  Zhang Mingjian,et al.  Comparative observation of the changes in serum lipid peroxides influenced by the supplementation of vitamin E in burn patients and healthy controls , 1992 .

[59]  C. Long,et al.  Ascorbic acid dynamics in the seriously ill and injured. , 2003, The Journal of surgical research.

[60]  M. Berger,et al.  Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. , 2007, The American journal of clinical nutrition.

[61]  M. Berger,et al.  Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects , 2007, Intensive Care Medicine.

[62]  M. Berger,et al.  Copper, selenium, and zinc status and balances after major trauma. , 1996, The Journal of trauma.

[63]  D. Acuña-Castroviejo,et al.  Melatonin and nitric oxide , 2005, Endocrine.