What is the significance of the Energize trial in burn patient care, particularly regarding nutritional support?

The Significance of the RE-ENERGIZE Trial in Burn Patient Care

The RE-ENERGIZE trial challenges previous recommendations for glutamine supplementation in burn patients, showing no mortality benefit or reduction in hospital length of stay, which should prompt reconsideration of routine glutamine supplementation in burn care protocols. 1

Nutritional Management in Burn Patients

Burn injuries trigger a profound hypermetabolic response that can persist for up to 2 years post-injury, with resting metabolic rates reaching up to 180% of baseline in the first week and remaining elevated for months 2. This metabolic derangement necessitates specialized nutritional support to prevent catabolism, improve outcomes, and reduce mortality.

Timing and Route of Nutrition

• Early initiation is critical: Nutritional support should begin within 12 hours after burn injury 3
• Enteral route preferred: Early enteral nutrition (EN) within 24 hours has been shown to:
  • Decrease muscle protein catabolism
  • Improve wound healing
  • Decrease ICU and hospital length of stay
  • Diminish rates of sepsis
  • Decrease infectious load
  • Decrease risk of Curling ulcer formation 2

Nutritional Requirements

• Energy needs:

  • Acute phase: 20-25 kcal/kg/day
  • Recovery phase: 25-30 kcal/kg/day 3
  • Best assessed through serial indirect calorimetry 2
  • When unavailable, the Toronto formula is the most accurate proxy 2

• Protein requirements:

  • 1.5-2 g/kg/day for adults 2, 3
  • Higher protein intake (1.5-2 g/kg/day) increases protein synthesis and reduces negative nitrogen balance 2
  • Protein rates exceeding this have not demonstrated additional benefits 2

• Carbohydrate management:

  • Careful monitoring required as excess carbohydrates can cause hyperglycemia
  • Hyperglycemia exacerbates inflammation, muscle breakdown, and excess fat production 2
  • Insulin administration can improve lean body mass, bone mineral density, donor site healing, and decrease length of stay, though requires careful monitoring for hypoglycemia 2

The RE-ENERGIZE Trial and Glutamine Supplementation

The RE-ENERGIZE trial represents a significant advancement in burn nutrition research:

• Study design: Multicentre, double-blind, randomized clinical trial involving 80 tertiary ICU burn centers worldwide 1
• Intervention: Enteral glutamine 0.5 g/kg/day vs. isocaloric maltodextrin control 1
• Primary outcome: Six-month mortality 1

Despite previous recommendations for glutamine supplementation in burns involving >20% body surface area (as per 2018 ESPEN guidelines), the RE-ENERGIZE trial found:

• No reduction in time to discharge from hospital
• No differences in 6-month mortality
• No differences in hospital length of stay
• No reduction in incidence of bacteremia compared to placebo 2

This contradicts earlier studies that suggested glutamine supplementation could decrease rates of infection, hospital length of stay, and mortality in severe burns 2. However, many of these earlier studies had significant flaws in design and outcomes 2.

Importance of Adequate Nutritional Support

The importance of meeting nutritional targets cannot be overstated:

• International observational data shows that mechanically ventilated burn patients develop substantial energy and protein deficits 4
• Greater nutritional deficits are associated with increased mortality:
  • Energy deficit/100 kcal: odds ratio for death 1.10 (p=0.028)
  • Protein deficit/10 g: odds ratio for death 1.16 (p=0.037) 4

Nutritional Risk Assessment

The modified Nutrition Risk in Critically Ill (mNUTRIC) Score has been validated in burn patients:

• Patients with high mNUTRIC scores (≥5) have:
  • Higher mortality (61% vs. 19%, p=0.001)
  • Longer time to discharge alive (>90 vs. 64 days, p<0.0001) 5
• Increased calorie intake was associated with lower mortality and faster discharge, but only in the high mNUTRIC group 5

Micronutrient Considerations

• Thermal injuries cause significant oxygen-free radical generation and endothelial injury
• Supplementation of vitamins A, C, D, and minerals (iron, copper, selenium, zinc) may improve wound healing and immune function 2
• Supplementation of calcium, magnesium, and vitamins has been shown to lower risk for wound infection, sepsis, and prolonged hospitalization 2

Common Pitfalls in Burn Nutrition Management

• Delayed initiation: Failing to start nutritional support within the first 24 hours
• Inadequate assessment: Not using indirect calorimetry or appropriate formulas to determine energy needs
• Overfeeding carbohydrates: Leading to hyperglycemia and associated complications
• Interruptions in feeding: Often due to operative procedures, leading to significant energy and protein deficits 4
• Relying on outdated glutamine recommendations: Continuing to provide routine glutamine supplementation despite newer evidence questioning its benefit 2

In conclusion, while early enteral nutrition remains the cornerstone of burn care, the RE-ENERGIZE trial has significantly impacted our understanding of glutamine supplementation in this population, suggesting a need to reconsider its routine use. Individualized nutritional assessment using tools like the mNUTRIC score and careful monitoring of nutritional adequacy are essential to improve outcomes in burn patients.