Refractory Hypoglycemia and Sulfonylurea Intoxication

Approach to Refractory Hypoglycemia

  • Decreased Gluconeogenesis
    • Hormone deficiency: Cortisol, Glucagon, Epinephrine
    • Critical illness: Hepatic, renal, or cardiac failure
    • Malnourishment
  • Increased Consumption
    • Critical illness: Sepsis!
  • Hyperinsulinism
    • Endogenous: Insulinoma, insulin secretagogue (such as sulfonylurea), insulin autoimmune hypoglycemia
    • Exogenous: Accidental, surreptitious hypoglycemia

Sulfonylurea (SFU) Poisoning

  • Mechanism of Action of SFU: Inhibits ATP-sensitive potassium channels in pancreatic beta cell membranes, leading to elevated intracellular potassium levels. This leads to depolarization and subsequent calcium influx, which activates the secretory system that releases insulin!
  • Pharmacokinetics: In overdose, onset of action remains unchanged, but duration of action increases! Peak plasma concentrations are achieved within 8 hours of acute ingestion, but delayed in overdose.
  • Metabolism: Metabolized by liver mostly, but some agents have active metabolites that are renal excreted
  • Treatment:
    • Octreotide: Works via a G-protein mediated decrease in calcium influx through voltage0gated channels in pancreatic beta islet cells, leading to diminished calcium-mediated insulin release. : May be given as an IV bolus over several minutes or by continuous IV infusion (for 24 hours)
    • Glucagon: Raises serum glucose levels slightly and may be used as a temporary measure while access is being obtained.
    • Dextrose Containing Solutions: D10W, D25W, D50W

Pearl on Ketosis and Hypoglycemia: Thanks to Kresh, for the pearl on ketosis and hypoglycemia. Ketosis is a natural process by which fatty acids are oxidized and exported to peripheral tissues for use as an energy source. Normally, presence of ketones implies that lipid metabolism has been appropriately activated and that the pathway of lipid degradation is in-tact. The absence of ketosis in a patient with hypoglycemia is abnormal and suggests a diagnosis of hyperinsulinism or an inborn error of fat energy metabolism.

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