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

What now???

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