Sulfonylurea Poisoning

Sulfonylureas (glibenclamide, glimepiride, gliclazide, glipizide, tolbutamide) stimulate insulin release by closing ATP-sensitive potassium channels in pancreatic beta cells, independent of glucose level. Overdose causes severe, prolonged hypoglycemia. A single tablet can cause hypoglycemia lasting over 24 hours in a child.

Duration depends on the drug: tolbutamide 6 to 12 hours, glipizide and gliclazide 12 to 24 hours, glibenclamide and glimepiride 24 to 72 hours or more (active metabolites). Renal failure prolongs the effect because active metabolites accumulate. Onset is typically 1 to 8 hours after ingestion, delayed for up to 24 hours with some preparations.

Therapeutic hypoglycemia occurs in older patients with poor oral intake, kidney or liver disease, and interacting drugs (fluoroquinolones, trimethoprim-sulfamethoxazole, clarithromycin, fluconazole, warfarin, salicylates). Complications: neuroglycopenic brain injury, seizures, arrhythmia, myocardial ischemia and recurrent hypoglycemia after initial correction.

• Adrenergic features: sweating, tremor, palpitations, anxiety, hunger
• Neuroglycopenic features: confusion, behavioral change, blurred vision, weakness, seizures, coma, focal deficits
• Recurrent hypoglycemia after treatment with dextrose
• Children: lethargy, irritability and seizures
• Red flags: coma, seizures, recurrent hypoglycemia, glucose under 2.5 mmol/L, and renal impairment

1. Capillary and venous glucose at presentation, then hourly. Hypoglycemia is glucose under 3.0 mmol/L (under 54 mg/dL), and severe when consciousness is altered.
2. Whipple triad: symptoms, low glucose and relief with glucose.
3. Electrolytes (including potassium), creatinine, liver tests, blood gases.
4. Insulin and C-peptide, and a sulfonylurea screen drawn during hypoglycemia, to separate sulfonylurea (raised insulin and C-peptide) from exogenous insulin (raised insulin, low C-peptide).
5. Paracetamol and salicylate levels, and an ECG.

Differentials: insulin overdose, insulinoma, adrenal insufficiency, sepsis, liver failure, alcohol-related hypoglycemia, other hypoglycemic drugs.

1. Immediate glucose: 50% dextrose 25 to 50 mL IV (children 10% dextrose 2 to 5 mL/kg), or oral carbohydrate if alert.
2. Maintenance: 10% dextrose infusion at 100 to 150 mL/h (children 5 mL/kg/h), titrated to glucose of 5 to 8 mmol/L. Avoid excessive dextrose, which stimulates more insulin secretion and causes rebound hypoglycemia.
3. Octreotide (the antidote of choice for recurrent hypoglycemia): 50 micrograms IV or SC every 6 hours (children 1 microgram/kg every 6 hours, maximum 50 micrograms), continued for 24 hours, or an infusion of 25 micrograms/h. Octreotide inhibits insulin secretion. Monitor for bradycardia and QT prolongation.
4. Glucagon 1 mg IM or IV has a short effect and often causes rebound hypoglycemia, so it is of limited value in this poisoning.
5. Diazoxide 3 to 8 mg/kg a day orally in 3 divided doses is an alternative when octreotide is unavailable.
6. Decontamination: activated charcoal 50 g orally (children 1 g/kg, maximum 50 g) within 1 to 2 hours for an alert patient with a protected airway.
7. Electrolytes: potassium usually falls after glucose and insulin release, so replace when below 3.5 mmol/L.
8. Seizures: treat hypoglycemia first, then lorazepam 4 mg IV (children 0.1 mg/kg).
9. Observation: admit for at least 24 hours, and for 24 hours after the last hypoglycemic episode without dextrose or octreotide. Monitor glucose hourly. Children need at least 12 hours of normoglycemia without dextrose.

Follow-up: review the diabetes treatment plan, renal function and interacting drugs. Counsel on regular meals, glucose monitoring and safe storage. Psychiatric assessment for intentional overdose.