What is the primary source of fuel in sepsis?

From the Guidelines

The main source of fuel in sepsis is glucose (option A). During sepsis, the body undergoes significant metabolic changes characterized by hypermetabolism and increased energy expenditure. Despite adequate glucose availability, septic patients develop insulin resistance and hyperglycemia, as noted in a recent study 1. The body preferentially uses glucose through aerobic glycolysis (even in the presence of oxygen), known as the Warburg effect, to rapidly generate energy for the immune response and cellular functions during this critical illness. This metabolic shift occurs because glucose provides a quick energy source needed to combat infection, though it is less efficient than normal aerobic metabolism. While fatty acids, ketones, and amino acids can serve as alternative fuel sources in other conditions, glucose remains the primary substrate utilized during the hypermetabolic state of sepsis, with the body often unable to effectively utilize these alternative fuels due to the metabolic derangements that occur during the septic response. Additionally, a study on clinical nutrition in the intensive care unit 1 supports the importance of glucose as a primary energy source, highlighting the need for early and progressive enteral nutrition in septic patients to meet their energy needs. Key points to consider include:

• Hyperglycemia is a common metabolic dysregulation in sepsis patients 1
• Glucose is redirected to immune cells promoting aerobic glycolysis and immune function 1
• Excessive immune activation as a result of enhanced glycolysis can actually do more harm than good 1
• Early and progressive enteral nutrition should be used in septic patients after hemodynamic stabilization 1

From the Research

Main Source of Fuel in Sepsis

• The main source of fuel in sepsis is glucose, as sepsis is associated with alterations in glucose metabolism 2, 3.
• Glucose administration is not associated with significant changes in plasma catecholamine concentrations in patients with sepsis 2.
• The wound and regenerating tissue require large amounts of glucose for glycolysis, and hyperglycemia provides a glucose gradient between plasma and tissue high enough for extraction of sufficient glucose 3.
• Other sources of fuel, such as fatty acids and ketones, are also utilized in sepsis, but to a lesser extent 4, 3.
• Amino acids are also required for the synthesis of acute-phase proteins and for the regeneration of the wound and rapidly proliferating white and red blood cells 3.

Metabolic Changes in Sepsis

• Sepsis is characterized by profound changes in systemic and cellular metabolism that disrupt normal metabolic homeostasis 5.
• Lactate, a metabolite of anaerobic metabolism, is the most widely used ICU biomarker and is incorporated into multiple management algorithms 5.
• Glycolysis is up-regulated in hyperinflammatory cells, whereas in immune tolerance, it is often down-regulated 4.
• The pentose phosphate pathway is up-regulated during acute hyperinflammatory responses, whereas fatty acid β-oxidation is increased later during sepsis and is associated with an anti-inflammatory (M2) phenotype of macrophages 4.