How does Propofol (propofol) affect insulin and glucose metabolism?

Propofol's Effects on Insulin and Glucose Metabolism

Propofol can cause hyperglycemia by inducing systemic insulin resistance in skeletal muscle, cardiac muscle, and liver, while paradoxically enhancing insulin secretion from pancreatic β-cells through its effects on voltage-dependent potassium channels. 1, 2

Mechanisms of Propofol's Effects on Glucose Metabolism

Effects on Insulin Secretion

• Propofol enhances insulin secretion from pancreatic β-cells by:
  • Blocking stromatoxin-1-sensitive voltage-dependent K+ channels (Kv2) in pancreatic β-cells 2
  • This blockade leads to membrane depolarization, increased Ca2+ entry, and subsequent insulin secretion 2
  • The effect is glucose-dependent, meaning propofol's enhancement of insulin secretion is more pronounced in the presence of glucose 2

Effects on Insulin Resistance

• Despite increased insulin secretion, propofol induces systemic insulin resistance by:
  • Decreasing insulin-stimulated glucose uptake in skeletal and cardiac muscles 1
  • Attenuating insulin-mediated suppression of hepatic glucose output 1
  • Increasing free fatty acid (FFA) levels, which can contribute to insulin resistance 3

Clinical Implications

Hyperglycemia Risk

• Blood glucose levels tend to increase during propofol anesthesia compared to the conscious state 3, 4
• Propofol attenuates glucose metabolism, as evidenced by prolonged half-life of plasma glucose 3
• In diabetic patients undergoing surgery, propofol may cause less hyperglycemia compared to inhalational anesthetics like isoflurane 4

Metabolic Considerations

• Propofol is formulated as an oil-in-water emulsion containing 10% soybean oil 5
• Prolonged infusions (>3 days) may lead to hypertriglyceridemia with potential risk of acute pancreatitis 5
• Monitoring of serum triglyceride levels is recommended during extended propofol use 5

Propofol Infusion Syndrome

• Rare but potentially fatal complication characterized by metabolic acidosis, hypertriglyceridemia, hypotension, and arrhythmias 5
• Associated with high-dose, prolonged administration of propofol 6
• Early recognition and discontinuation of propofol in patients with suspected PRIS is critically important 6

Perioperative Management Considerations

Blood Glucose Monitoring

• Regular monitoring of blood glucose levels is essential during propofol anesthesia, especially in diabetic patients
• Target blood sugar level of <10 mmol/L (180 mg/dL) is recommended to avoid hypoglycemia 6
• Measurements should be carried out in arterial or venous blood rather than capillary blood, which may overestimate blood sugar levels 6

Insulin Management

• If insulin is required during propofol anesthesia:
  • Ultra-rapid short-acting insulin analogues are preferred, administered continuously via IV 6
  • Always give insulin in association with IV glucose (equivalent of 4 g/h) and electrolytes 6
  • Monitor blood glucose every 1-2 hours and potassium every 4 hours 6

Practical Considerations

• Propofol may be preferred over inhalational anesthetics in diabetic patients requiring strict glycemic control 4
• In patients requiring antiemetic therapy, be aware that dexamethasone (often used as an antiemetic) can cause hyperglycemia, especially at higher doses 6
• For diabetic patients, consider anesthesia strategies that minimize nausea/vomiting risk (propofol rather than halogenated agents) 6

Caveats and Pitfalls

• The lipid emulsion in propofol can support microbial growth, requiring strict aseptic technique 5
• Propofol is contraindicated in patients with allergies to eggs, soy, or sulfites 5
• Pain on injection is common (up to 30% of patients) when administering IV bolus 6
• The cardiovascular effects of propofol include decreases in cardiac output, systemic vascular resistance, and arterial pressure 6