What metabolic changes occur during anesthesia?

Metabolic Changes During Anesthesia

During anesthesia, the body shifts from a fed to a fasted metabolic state characterized by decreased whole body protein and glucose metabolism, with surgical stress superimposing a catabolic response that includes hyperglycemia, insulin resistance, protein breakdown, and mobilization of alternative fuel sources.

Core Metabolic Alterations

Glucose Metabolism

• Whole body glucose production (rate of appearance) decreases during anesthesia and surgery, independent of the anesthetic technique used 1
• Glucose clearance is reduced during the anesthetic period 1
• Surgery triggers rapid hyperglycemia through stress hormone activation, particularly cortisol and catecholamines, even as overall glucose turnover decreases 2, 1
• The hyperglycemic response persists up to 12 hours postoperatively and is significantly correlated with plasma adrenaline levels at the end of surgery 2

Protein Metabolism

• Whole body protein synthesis decreases during anesthesia and surgery 1
• The rate of appearance of leucine (a marker of protein breakdown) decreases during surgery 1
• Leucine oxidation is reduced during the anesthetic period 1
• A strong correlation exists between glucose production and protein breakdown (r = 0.755), indicating integrated metabolic suppression 1
• Plasma albumin and total protein concentrations decrease significantly during anesthesia and surgery 3

Lipid and Alternative Fuel Mobilization

• Plasma free fatty acids, total ketone bodies, and glycerol concentrations increase significantly by the end of surgery, reflecting lipolysis and mobilization of gluconeogenic substrates 2
• Blood lactate and pyruvate increase during surgery, indicating anaerobic metabolism and stress response 2, 3

Hormonal Regulation

Stress Hormone Response

• Plasma adrenaline and noradrenaline increase significantly in response to surgery, driving the catabolic state 2
• Plasma cortisol concentrations increase during surgery 1, 3
• The insulin/glucose ratio decreases significantly at the end of surgery, indicating relative insulin resistance 2

Insulin and Glucagon Dynamics

• In term neonates, plasma insulin remains unchanged during surgery but increases significantly throughout the postoperative period 2
• Plasma glucagon levels remain unchanged during surgery but decrease by 24 hours postoperatively 2
• Blood glucose correlates with plasma glucagon at 6 hours postoperatively 2

Surgical Stress vs. Anesthesia Alone

A critical distinction: anesthesia alone causes minimal metabolic changes, while surgical stress drives the major metabolic derangements 3

• Enflurane anesthesia alone for 2 hours produces no significant effect on circulating metabolite concentrations 3
• Most changes in glucose, lactate, and other metabolites occur rapidly after surgical incision begins, not from anesthetic agents themselves 3
• CO₂ production decreases by approximately 9% during anesthesia and surgery, returning toward baseline during recovery 3

Insulin Resistance and Surgical Stress

Major surgery elicits pituitary and sympathetic nervous system activation, leading to insulin resistance as the pivotal metabolic derangement 4

• Insulin resistance results in poor glucose uptake, hyperglycemia, reduced glycogen storage in muscle and liver, and subsequent muscle breakdown 4
• Insulin resistance is associated with increased morbidity, mortality, and hospital stay 4
• Pre-operative carbohydrate loading (shifting patients from fasted to fed state) can blunt postoperative insulin resistance by approximately 23% (insulin sensitivity falling 45% vs. 68% in controls) 4

Metabolic State Transition

The traditional overnight fasting approach shifts patients into a catabolic, fasted metabolic state that amplifies surgical stress responses 4

• Allowing clear fluids until 2 hours before anesthesia and carbohydrate loading can alter metabolism from fasting to fed state 4
• Pre-operative carbohydrate drinks increase liver glycogen by approximately 65% and improve postoperative protein balance 4
• The fed state induced by carbohydrate loading improves preservation of lean body mass and muscle strength 4

Energy Metabolism

• CO₂ production and overall metabolic rate decrease during anesthesia, reflecting reduced cellular energy demands 3
• Anesthetic agents are metabolized primarily in the liver through oxidative reactions catalyzed by P-450 cytochromes 5
• The catabolic state during surgery is characterized by glycogenolysis, gluconeogenesis, lipolysis, and mobilization of gluconeogenic substrates 2

Clinical Implications

Common Pitfalls

• Assuming anesthetic agents cause the metabolic derangements: The surgical stress response, not anesthesia itself, drives most metabolic changes 3
• Maintaining traditional prolonged fasting periods that worsen the catabolic state and insulin resistance 4
• Failing to recognize that total parenteral nutrition given just before surgery and certain anesthetic agents (thiopentone) can significantly augment the hyperglycemic response 2

Optimization Strategies

• Consider pre-operative carbohydrate loading to shift patients from fasted to fed metabolic state, reducing insulin resistance and improving postoperative outcomes 4
• Allow clear fluids until 2 hours before anesthesia to prevent dehydration and improve patient metabolic status 4
• Recognize that prevention of metabolic derangements through anesthetic or hormonal manipulation may improve clinical outcomes 2