Sulfonylurea toxicity

Background

  • Sulfonylureas are a commonly prescribed oral diabetes medication, and include glyburide, glimepiride, glipizide chlorpropamide, tolazamide
  • Inhibit potassium efflux from pancreatic beta cells→ increased insulin release

Clinical Features

  • Hypoglycemia
    • Can occur at therapeutic doses in renally impaired patients
    • Hypoglycemia often prolonged and severe
    • Onset within 8 hours of ingestion
  • Pediatrics: one pill can kill!!

Differential Diagnosis

Differential diagnosis of hypoglycemia

Hypoglycemia

Drugs

Systemic Illness

Malignancy

  • Insulinoma
  • Non-islet cell
  • Insulin/receptor autoantibodies
  • High tumor burden

Other

Precipitants of anti-hyperglycemic induced hypoglycemia

  • Decreased glucose
    • Missed meal
    • Consumption (exercise, illness)
  • Increased drug
    • Error (patient, provider)
    • Intentional overdose
    • Increased availability
      • Hepatic failure
      • Renal failure
      • Drug interaction

Evaluation

  • Hypoglycemia + known or suspected ingestion
  • BMP, creatinine, decrease in renal clearance may have led to toxicity
  • Serial POC glucose measurements
  • Routine ingestion labs if suspect intentional OD

Management

Hypoglycemia from Sulfonylureas[1][2]

Activated charcoal[3]

  • Administer activated charcoal, preferably within 1 hr of ingestion
  • Multiple doses may be beneficial, especially for glipizide

Glucose Treatment

  • Initial Therapy regardless of known cause
Adults
  • 50mL D50W bolus
  • Start a D10 1/2NS drip (100mL/hr)
Children
  • 1mL/kg of D50W OR
  • 2mL/kg D25W OR 5-10mL/kg D10W
  • Neonate: 5-10 mL/kg D10W

Octreotide[4]

  • Theoretical benefit to reduce risk of recurrent hypoglycemia
  • Hyperpolarization of the beta cell results in inhibition of Ca influx and prevents insulin release
  • 50-100 mcg subcutaneous in adults with repeat dosing Q6hrs
  • 2 mcg/kg (max 150mcg) subcutaneously Q6hrs should be used in children
  • Continuous infusion of 50-125 mcg/hr is an alternative in adults
  • Administer octreotide for 24 hours, then after discontinuing, monitor for hypoglycemia for another 24 hours

Special Considerations

  • Glucagon 5mg IM may be used as temporizing measure, e.g. while obtaining IV access
    • Dependent on glycogen stores which may be depleted in prolonged hypoglycemia
    • Also short duration of action
    • Caution in using glucagon drip
      • Glucagon also has an insulin-releasing effect
      • May subsequently cause initial paradoxical hypoglycemia

Disposition

  • Admit

See Also

External Links

References

  1. Rowden AK, Fasano CJ. Emergency management of oral hypoglycemic drug toxicity. Emerg Med Clin N Am 2007; 25:347-356
  2. Howland MA. Antidotes in Depth: Octreotide. In: Flomenbaum NE, Goldfrank LR, Hoffman RS et al, eds: Goldfrank’s Toxicologic Emergencies. New York NY, 2006;770-773
  3. Tran D et al. Oral Hypoglycemic Agent Toxicity Treatment & Management. Jul 14, 2015. http://emedicine.medscape.com/article/1010629-treatment#showall.
  4. Fasano CJ et al. Comparison of Octreotide and standard therapy versus standard therapy alone for the treatment of sulfonylurea-induced hypoglycemia. Ann Emerg Med 2008; 51:400-406

Authors:

Ross Donaldson