What is the role of glutamine (glutamine) supplementation in patients with traumatic brain injury (TBI)?

Glutamine Supplementation in Traumatic Brain Injury

Direct Recommendation

Glutamine should be added to standard enteral nutrition formulas in trauma patients, including those with traumatic brain injury, at doses of 0.2-0.57 g/kg/day. 1

Evidence-Based Rationale

Guideline Support for Trauma Patients

• ESPEN guidelines provide Grade A recommendation for glutamine supplementation in trauma patients receiving enteral nutrition. 1

• One published study of 72 trauma patients demonstrated significantly lower rates of bacteremia, pneumonia, and sepsis with glutamine supplementation added to standard enteral formulas. 1

• The recommendation specifically applies when glutamine is added to standard formulas, not as part of complex immune-modulating formulas. 1

Dosing Strategy

For parenteral nutrition: 0.2-0.57 g/kg/day of glutamine (equivalent to 10-30 g glutamine/24 hours or 0.3-0.6 g/kg/day of alanyl-glutamine dipeptide). 1, 2

Standard dosage: 0.5 g/kg/day of L-alanyl L-glutamine dipeptide when exclusive parenteral nutrition is required. 2

Safety Considerations in TBI

• Concerns about glutamate neurotoxicity in head trauma patients have not been substantiated—cerebral glutamate levels are not affected even in head trauma patients receiving glutamine supplementation. 1

• Glutamine supplementation has been safely tolerated in doses of 10-30 g/24 hours with restoration of plasma levels and no harmful effects reported in critically ill patients. 1

Metabolic Rationale in TBI

• TBI patients demonstrate profound hypoglutaminemia, with cerebral outflow of glutamine reduced to only 6% of total amino acid output compared to 73% in normal patients. 3

• Nutritional support improves net release of glutamine from the brain, suggesting supplementation may be beneficial to support systemic requirements in severe head injuries. 3

• A significant linear relationship exists between glutamine (product) and glutamate (precursor) in jugular venous samples, indicating active cerebral glutamine metabolism. 3

Clinical Outcomes in TBI

• Preliminary evidence suggests immune-enhancing nutrition (containing glutamine, arginine, and omega-3 fatty acids) in TBI patients reduces bloodstream infections (10.3% vs 19.3%, p<0.05) and improves prealbumin levels throughout hospitalization. 4

• Prealbumin levels were significantly higher at weeks 2-4 in TBI patients receiving immune-enhancing nutrition (week 2: 22.2 vs 17.4, p=0.006; week 3: 24.6 vs 20.1, p=0.04). 4

Critical Contraindications

Do not use high-dose parenteral glutamine in critically ill patients with acute kidney injury or chronic kidney disease—this is associated with increased mortality. 2

• A large multicenter RCT showed high-dose glutamine in critically ill patients with organ dysfunction increased mortality risk. 2

• The mortality benefit seen in earlier meta-analyses (RR 0.67, CI 0.48-0.92) applies specifically to critically ill patients without organ failure requiring parenteral nutrition. 1, 2

Implementation Algorithm

Step 1: Assess Patient Eligibility

• Confirm diagnosis of traumatic brain injury requiring nutritional support. 1
• Screen for contraindications: acute kidney injury, chronic kidney disease, or multi-organ failure. 2

Step 2: Determine Route of Administration

• Enteral route preferred: Add glutamine to standard enteral formula if gut function permits. 1
• Parenteral route: Use glutamine-containing dipeptides (alanyl-glutamine or glycyl-glutamine) if exclusive parenteral nutrition required. 1, 2

Step 3: Dosing

• Enteral: Follow trauma patient guidelines with glutamine-supplemented standard formulas. 1
• Parenteral: 0.2-0.57 g/kg/day of glutamine, typically 0.5 g/kg/day of alanyl-glutamine dipeptide. 1, 2

Step 4: Monitor

• Ensure nutritional goals achieved within 5-7 days of injury per TBI management guidelines. 5
• Monitor for infectious complications, particularly pneumonia and bacteremia. 4
• Assess renal function regularly; discontinue if organ dysfunction develops. 2

Important Caveats

• The evidence for glutamine in heterogeneous critically ill patients is insufficient and potentially harmful, but trauma patients (including TBI) represent a specific subgroup with demonstrated benefit. 1, 6

• Glutamine supplementation should be part of standard nutrition formulas, not complex immune-modulating formulas that may have negative effects in severely ill patients who cannot tolerate adequate volumes. 1

• Continuous renal replacement therapy increases glutamine loss by 4-7 g/day, potentially increasing supplementation needs in this context. 1