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

• Anti-hyperglycemic
  • Insulin
  • Oral secretagogue
    • Sulfonylurea toxicity
• Other
  • EtOH
  • B-blocker
  • ACEI
  • Acetaminophen (OD)

Systemic Illness

• Critical Illness
  • Sepsis
  • MI
• Organ Failure
  • Hepatic failure
  • Renal failure
• Endocrinopathy
  • Adrenal insufficiency
• Seizure
• Inborn errors of metabolism

Malignancy

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

Other

• Artifactual
  • Specimen collection
  • Consumption
    • Leukemia
    • Erythrocytosis
    • Hemolytic disease
• Post-surgical
  • Gastric bypass
  • Gastrectomy
  • Pyloroplasty
• Starvation
  • Anorexia nervosa

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
  • Acetaminophen and salicylate levels
  • ECG, look for QRS widening and QTc prolongation

Management

Hypoglycemia from Sulfonylureas

Activated charcoal

• 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

• 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

• Hypoglycemia
• Diabetes medications