Sulfonylurea toxicity

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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

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
  • Because of prolonged effect, not appropriate to discharge from ED even with normal glucose and patient tolerating PO, as hypoglycaemia may recur over 24h or more

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