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Engela Francis RD(SA)
Department of Dietetics
Steve Biko Academic Hospital
DISCUSSION TOPICS
Importance of Glutamine in the Critically ill patient
REDOX trail
What now? The way forward
GLUTAMINE IN ICU Conditionally essential AA under stress / catabolic
conditions
GLN levels depleted within 24-48hr post injury
Major metabolic fuel for enterocytes and colonocytes = improves GIT function
Major metabolic fuel for immune competent cells = improves immune function (GALT)
Most important substrate for renal ammoniogenesis (regulates acid base balance)
GLUTAMINE IN ICU Increases protein synthesis and N2 balance
Infectious complications
ICU LOS and Hospital LOS
• GLN deficiency in critical illness predicts
mortality
• GLN supplementation of TPN mortality with 29%
GLUTAMINE IN ICU • GLN plays key role in enhancing the synthesis
of HSP
• HSP is essential to cellular recovery following stress/injury
• HSP protect against organ failure
• Critical illness shows tissue HSP deficit
• GLN required for activation of the genes for HSP expression
• Decreased GLN = Decreased HSP
GLUTAMINE IN ICU Clinical Practice Recommendations on Glutamine
EN: Burns and Trauma
IV with PN: Critically Ill
Year Route Dose
ESPEN 2009 2006
IV with PN EN
0.2 – 0.4 g/kg/d
ASPEN 2011 IV with PN >0.2 g/kg/d
CCCPG 2009 2009
IV with PN EN
0.2 – 0.57 g/kg/d
Glutamine was considered to be a miracle “drug” for the critically ill patient, and then came the REDOX trail
N Engl J Med 2013;368:1489-97
REDOX HYPOTHESIS
Supplementation with Glutamine and Antioxidants would reduce 28-day mortality in Critically Ill Patients
METHOD
Multicentre randomised blinded 2-by-2 factorial trail
40 ICU’s (Canada, USA and Europe)
REDOX STUDY DESIGN
1223 Adult ICU patients
2 or more organ failure (MOF)
Including renal failure
Supplementation started within 24 hours of ICU admission
REDOX STUDY PATIENTS
Characteristic Glutamine (N 301)
Age 62.5±15.0 (19.0 – 91.5)
BMI - range 29.9±8.9 (16.7 – 70.4)
APACHE II score - range 26.6±7.6 (8.0 – 48.0)
Admission category – no.(%) Medical Surgical
238 (79.1) 63 (20.9)
Inclusion criteria – no.(%) PAO2:FIO2 ratio ≤300 Clinical hypoperfusion Renal dysfunction Platelet count ≤50x10₉/litre
285 (94.7) 278 (92.4) 117 (38.9) 21 (7.0)
No. of failed organs – no.(%) 1 2 3 4
2 (0.7) 206 (68.4) 85 (28.2) 8 (2.7)
REDOX SUPPLEMENTATION
IV GLN: 0,35g/kg IBW per day
Enteral GLN: 30g/d
Example: IBW = 70kg
• GLN = 24.5 g + 30 g = 54.5 g/d
• = 0.8g/kg per day
Supplementation administered separately from standard nutrition (Canadian Critical Care Nutrition practice guidelines)
REDOX RESULTS
Supplements (GLN):
IV – 89.1% Enteral – 70.9%
Still providing GLN = 0.62 g/kg per day
Nutrition:
49.9% Energy (± 13 kcal/kg per day)
45.4% Protein (± 0.6 g/kg per day)
REDOX
RESULTS
Glutamine supplementation associated with increased 28-day mortality.
REDOX DISCUSSION
GLN supplementation higher than previous recommendations (0.35 – 0.5g/kg per day)
Patients – MOF + Shock
Most pt’s received TEN previous studies TPN
Assumption that GLN levels are reduced in ICU pt’s (<420 µmol/L associated with increased mortality)
GLN group: GLN levels: day 1 – 494.5 ; day 4 – 717.6 ; day 7 – 608.6 µmol/L
THE WAY FORWARD 2013: Parenteral Glutamine Supplementation in
critical Illness: A systemic Review. Wischmeyer PE, Dhaliwal R, McCall M, Ziegler T, Heyland D
Parenteral GLN supplementation in ICU pt’s with Pancreatitis, Trauma, Burns and Sepsis
8 level 1 and 19 level 2 studies: Parenteral GLN supplementation associated with reduction in overall mortality
Infectious complications, ICU LOS, Hospital LOS
THE WAY FORWARD 2013: Canadian Clinical Practice Guidelines
EN: 2 level 1 and 7 level 2 studies enteral GLN should be considered in burns and trauma (Should be avoided in MOF and shock)
EN dose: 0.3 – 0.5 g/kg/d
PN: 9 level 1 and 19 level 2 studies parenteral supplementation with GLN should be considered in critical ill pt’s excluding MOF and shock (down graded)
PN dose: 0.2 – 0.57 g/kg/d
THE WAY FORWARD 2014: The Truth about nutrition in ICU. Singer P,
Doig GS, Pichard C
PN GLN supplementation Grade A recommendation by ESPEN
Post REDOX: Avoid GLN supplementation in patients with renal failure or more than 2 organ failures
Underfeeding promotes catabolism and reduce immune and healing functions
High protein intake (1.5 g/kg/d) is recommended
CONCLUSION Glutamine should be used with caution, but
does show benefit in ICU patients when supplemented in PN
Glutamine should not be used in patients with MOF and patients in shock.
Glutamine should be avoided in renal and hepatic failure
Dose: 0.3 – 0.5 g/kg/d
REFERENCES A Randomized Trail of Glutamine and Antioxidants in
Critically Ill Patients. Heyland D, Muscedere J, Wischmeyer PE, et al. N Engl J Med 2013;368:1489-97
Supplementary Appendix to REDOX. NEJM.org
The truth about nutrition in the ICU. Singer P, Doig GS, Pichard C. Intensive Care Med 2014;40:252-255
Parenteral Glutamine Supplementation in Critical Illness: A Systemic Review. Wishmeyer PE, Dhaliwal R, McCall M, et al. 1522994
The evolution of nutrition in critical care: How much, how soon? Wishmeyer PE. Critical Care 2013;17(Suppl 1):S7
REFERENCES Immunonutrition: A South African perspective. Prins A,
Visser J. SAJCN 2012;25(3):95-110
ASPEN Position Paper: Parenteral Nutrition Glutamine Supplementation. Vanek VW, Matarese LE, Robinson M, et al. Nutr Clin Pract 2011;26:479-494
ESPEN Guidelines on Parenteral Nutrition: Intensive Care. Singer P, Berger MM, Van der berghe G, et al. Clinical Nutrition 2009;1-14
Canadian Clinical Practice Guidelines. 2013. www.criticalcarenutrition.org
THANK YOU