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CLINICAL NUTRITION WEEK 2011: A SUMMARY OF RECOMMENDATIONS FOR GLUTAMINE AND ANTIOXIDANT SUPPLEMENTATION Cecilia Freeman RD, LD, CNSC Learning Objectives • Review the metabolic, immunological, and antiinflammatory functions of glutamine and antioxidants • Review the clinical benefits of supplementing with glutamine and antioxidants • Become familiar with supplementation guidelines Glutamine • The human body normally produces in sufficient amounts • Metabolic functions • Immunologic functions Metabolic Functions of Glutamine • Primary fuel for mucosal cells and immune cells • Precursor for the synthesis of substrates • Transports nitrogen between tissues for anabolic processes • Important for maintaining cell hydration Immunologic Functions of Glutamine • Energy source for leucocytes, lymphocytes, monocytes, and macrophages • Provides amino acids for synthesis of DNA and RNA • Promotes cytokine production by lymphocytes and macrophages, reduces release of pro-inflammatory cytokines Glutamine in Trauma • Patients having a higher plasma glutamine level have higher chance of survival compared to patients with lower glutamine levels • Oudemans-van Straaten et al, Intensive Care Med 2001 • Trauma patients experience a rapid decrease in concentrations of glutamine in muscle • Stehele et al, Klin. Em. 35, 1991 • Hammarqvist et al, Amino Acids 1994 • Low plasma glutamine correlates with higher APACHE II score and increased mortality • Oudemans-van Straaten et al, Intensive Care Med 2001 Enteral Glutamine Pros • Glutamine accounts for 35% of total metabolic requirements of enterocytes • Preserves gut barrier function by enhancing immune function • Decreases free radical availability by increasing glutathione Enteral Glutamine Cons • Difficult to deliver total daily dose because of intolerance problems or treatment/procedures • Reduction in the number of glutamine transport proteins on the surface of the gut during sepsis • Decreased absorptive function due to rapid turnover of enterocytes Dosing Burn/Trauma Patients 5-10 grams 4-5 x per day (0.40.5gm/kg/day) Parenteral glutamine probably better Medical/Surgical Intensive Care 0.35-0.5gm/kg/day Greatest benefit ≥ 0.5g/kg/day IV General Recommendations • Parenteral glutamine should be provided for all patients receiving parenteral nutrition • Enteral glutamine supplementation recommended for trauma and burn patients • For patients receiving enteral nutrition, parenteral glutamine might be supplemented Summary 0.3-0.5g/kg/day, starting within first 24 hours, for at least 7 days Improves clinical outcomes such as decreased episodes of pneumonia, bacteremia, and sepsis in trauma patients Houdijk et al, Lancet 1998 Importance of Antioxidants • Prevent lipid perioxidation • Co-factor for glutathione perioxidase • Supports catalase and superoxide dismutase Antioxidants • Antioxidant levels are low in critically ill and injured patients upon arriving to the ICU and remain low • Supplementation with ascorbic acid, αtocopherol, and selenium may prove beneficial in patients with intense inflammation and tissue damage following trauma/surgery Background All SIRS patients had below normal selenium Selenium replacement may attenuate the progression to MOF, speed recovery Bulgar E et al, Arch Surg 2001 Ascorbic acid and α-tocopherol may reduce incidence of infections complications Forceville X et Al, Crit Care Med 1998 Schorah C et al, Am J Clin Nutri 1996 Antioxidant supplementation may prevent MOF Bulgar E et al, Arch Surg 2001 Bichard C et al, CCM 1990 Supplementation in Critically Ill Surgery Patients • More vent free days in the antioxidant group • Decrease ICU-LOS, overall LOS in antioxidant group • 28 day mortality decreased in antioxidant group • Nathans A et al, Ann Surg 2002 Supplementation to facilitate ventilator weaning • Median mechanical ventilation time 15d placebo vs. 6 day in antioxidant group; p <0.05 • Concluded antioxidants are a safe, inexpensive and effective way to reduce days of mechanical ventilation • Concluded no additional benefit from Nacetylcysteine supplementation in patients receiving vitamin C + E • Howe et al, SCCM 2005 Selenium in sepsis • Prospective randomized, placebocontrolled, multicenter trial in Germany • 249 patients with severe SIRS, sepsis, or septic shock + APACHE III score >70 • 1000 mcg of sodium-selenite (bolus), then 14 days of 1000 mcg intravenously OR placebo Selenium in sepsis • Intention to treat analysis performed • 28 day mortality: 57% placebo, 42% selenium group (p=0.05) • Subgroup analysis: mortality rate significantly reduced in septic shock + DIC (p=0.01), APACHE III>102 (p=0.04), and ≥ 3 organ dysfunctions (p=0.03) • Angstwrum MA et al, Crit Care Med 2007 2008 Premier Research Paper Impact of High-Dose Antioxidants on Outcomes in Acutely Injured Patients 28% relative risk reduction in mortality Reduction in ICU and Hospital LOS JPEN July/August 2008 Summary Antioxidant levels are low in critically ill and injured patients upon ICU admission and remain low Supplementation is effective in raising levels Supplementation reduced infectious complications and inflammatory response Take Home Information Supplementation with these substances is proven to improve patient outcomes As clinicians we should include glutamine and antioxidant supplementation recommendations along with our nutrition support (TF/TPN) recommendations for appropriate patients Should we consider implementing protocols for glutamine and antioxidants in our facilities? Would a combination of supplementation with glutamine and antioxidants together be beneficial? [email protected] Question