What is the role of L-glutamine (L-glutamine) supplementation in critically ill patients in the Intensive Care Unit (ICU)?

L-glutamine Supplementation in Critically Ill ICU Patients

Parenteral L-glutamine supplementation at doses of 0.2-0.4 g/kg/day should be administered when parenteral nutrition is indicated in ICU patients, but enteral glutamine supplementation is not recommended for general critically ill populations except in burn and trauma patients. 1

Role of L-glutamine in Critical Illness

• Glutamine is the most abundant free amino acid in the body and becomes "conditionally essential" during critical illness as demand exceeds endogenous production 2
• Under normal conditions, glutamine is produced endogenously (primarily in skeletal muscle) at rates of 50-80g/24h for adults 1, 2
• During critical illness, plasma glutamine levels often fall due to increased utilization for immune function and tissue repair 1, 3
• Low plasma glutamine levels are associated with worse clinical outcomes in ICU patients 1, 2

Parenteral Glutamine Supplementation

Recommendations for Parenteral Nutrition

• When parenteral nutrition (PN) is indicated in ICU patients, the amino acid solution should contain 0.2-0.4 g/kg/day of L-glutamine (equivalent to 0.3-0.6 g/kg/day alanyl-glutamine dipeptide) 1
• Accumulated data from multiple studies involving 530 critically ill patients indicates a reduced mortality risk with PN containing glutamine (RR 0.67, CI 0.48-0.92, p=0.01) 1
• No studies of intravenous L-glutamine or dipeptide have shown harmful effects in critically ill patients at doses of 10-30g glutamine/24h 1
• Glutamine-containing dipeptides (alanyl-glutamine or glycyl-glutamine) provide stable and soluble alternatives to overcome the pharmaceutical limitations of L-glutamine 1, 2

Clinical Benefits of Parenteral Glutamine

• Parenteral glutamine supplementation has been associated with:
  • Reduced mortality 1, 4
  • Reduced infectious complications 1, 3
  • Improved glycemic control 1
  • Reduced length of hospital stay 1, 5
  • Reduced hospital costs 5

Enteral Glutamine Supplementation

Specific Patient Populations

• Enteral glutamine supplementation is recommended for:
  • Burn patients (Grade A recommendation) - associated with significant reductions in hospital mortality and length of stay 1, 6
  • Trauma patients (Grade A recommendation) - associated with lower rates of bacteremia, pneumonia, and sepsis 1

General ICU Population

• There are insufficient data to support enteral glutamine supplementation in surgical or heterogeneous critically ill patients 1
• Four studies in heterogeneous groups of critically ill patients found no significant differences in infectious complications, length of stay, or mortality 1
• A systematic review of enteral glutamine supplementation in critically ill patients showed no association with reduced hospital mortality, infectious complications, or ICU length of stay 6

Cautions and Contraindications

• Recent large-scale trials (REDOXS and MetaPlus) have raised concerns about glutamine supplementation in certain critically ill populations 7
• The REDOXS trial showed a trend toward increased 28-day mortality and significant increased hospital and 6-month mortality in those who received glutamine 7
• The MetaPlus trial noted increased 6-month mortality in the glutamine-supplemented group 7
• Caution should be exercised with indiscriminate use of glutamine supplementation for all critically ill patients 2, 7

Practical Considerations

• When dipeptide cannot be incorporated within the PN itself, it has been shown safe to administer through a peripheral line 1
• Continuous renal-replacement therapy may increase glutamine loss by 4-7 g/day, potentially enhancing the case for glutamine supplementation in this context 1
• High-dose or parenteral (>0.20-0.30 g/kg/day or ≥30 g/day) glutamine appears to demonstrate the greatest potential for benefit in critically ill patients 3

Summary of Evidence Quality

• The recommendation for parenteral glutamine supplementation is based on multiple clinical outcome studies, though each recruited modest numbers of patients 1
• The evidence for enteral glutamine in burn and trauma patients is strong (Grade A) 1
• The evidence against routine enteral glutamine in general ICU populations is consistent across multiple studies 1, 6