Glutamine in Critical Illness

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Glutamine in Critical Illness

• Shiva Sharma
• SHO Breast/Endocrine Surgery

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Contents

• Introduction
• Roles of Glutamine in the body
• Tissue Protection
• Anti-inflammatory regulation
• Preservation of metabolic function
• Glutamine as therapy

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• Leading cause of death in critically ill patients
  is sepsis
• 230,000 deaths in the USA each year secondary to
  sepsis
• Mortality rate from sepsis risen by 90 in last
  20years
• Development of multi-organ failure
• Organ dysfunction secondary to shock,
  inflammation, metabolic disturbances

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What is Glutamine?

• Non-essential amino acid
• Most abundant AA in the body
• 50 free AA in plasma
• Energy source
• Precursor to glutathione
• For nucleic acid synthesis
• Anti-oxidant effects
• Used for nitrogen transfer

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Roles

• Kidney
• Acid-base regulation
• Releases ammonia in urine
• Combines with proton to release bicarbonate into
  renal venous bed
• Immune response
• Fuel for monocytes, macrophages, lymphocytes
• Unable to synthesise, rely on plasma glutamine

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Roles of Glutamine
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Glutamine in Critical Illness

• Over last 15-20 years effects of glutamine
  studied in ICU setting
• Beneficial effects including decreased
  morbidity/mortality
• Patients in ICU in profound catabolic states
• Release of amino acids from muscle breakdown
• Glutamine however does not increase in critically
  ill patients

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• Decrease in plasma glutamine observed in
  critically ill patients
• Planas M, Schwartz S, Arbos MA, et al Plasma
  glutamine levels in septic patients. JPEN J
  Parenter Enteral Nutr 1993 17299300
• Low glutamine has also been associated with
  increased mortality in ICU patients
• Oudemans-van Straaten HM, et al Plasma glutamine
  depletion and patient outcome in acute ICU
  admissions. Intensive Care Med 2001 278490

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Mechanism

• Not fully understood
• ?signalling molecule to regulate gene expression
  and intracellular signalling
• Stress signal to the body increase cellular and
  immune defence

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Tissue Protection

• Enhancement of Heat Shock Proteins
• These proteins are vital to cellular response to
  stresses, and regulate the management of
  intracellular proteins
• Wischmeyer etal. performed a series of
  experiments in a rat model to show that glutamine
  enhanced HSP-70 in septic rats
• Metabolic dysfunction was decreased
• ARDS decreased
• Decreased Mortality

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• Ziegler TR etal. also went on to perform a pilot
  study Double blind trial looking at Glutamine vs
  Isonitrogenous control solution in ICU patients
  on TPN for gt5days
• Glutamine given as 0.5mg/kgday
• Showed increase in HSP-70 expression
• Decrease in ICU stay
• Ziegler TR, Ogden LG, Singleton KD, et al
  Parenteral glutamine increases serum heat shock
  protein 70 in critically ill patients. Intensive
  Care Med 2005 3110791086

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Anti-Inflammatory Regulation

• Activates peroxisome proliferation activated
  receptor-DNA binding sites
• This leads to attenuation of inflammatory
  response pathways through inhibitory
  transcription factors
• Glutamines acts on NF-kB signalling pathways
• ?HSP link, as HSP knockout mice loose this
  attenuation ability when glutamine administered
  after sepsis

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Metabolic Function

• Glutamine decreases insulin resistance
• Reduced hyperglycaemia in ICU patients
• Enhances release of insulin from Beta-cells
• Overall improved insulin sensitivity after
  administration
• Dechelotte P, 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. Crit Care Med 2006 34598604

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Glutamine as a Therapy

• Multiple advantages described to support
  glutamine administration
• Parenteral and enteral supplementation decrease
  mortality
• REDOXS study looking at glutamines ability to
  protect against injury, reduce inflammation,
  preserve metabolic function

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• Critical Care Connections Inc 2005 (Canadian
  Clinical Practice Guidelines) suggest
  supplementation of parenteral nutrition with
  glutamine and enteral glutamine for burns/trauma
  patients
• Possible role in patient nutrition
• Possible role as prophylaxis in surgery/ICU for
  prolonged admissions