There are 18.8 million people in the United States diagnosed with Type II diabetes (T2DM).¹ The mainstay of T2DM treatment is oral anti-diabetic therapy, and pediatric exposures may result from the significant number of homes with these medications. However, not all oral anti-diabetic agents produce hypoglycemia in overdose. Biguanides, thiazolidinediones, and alpha-glucosidase inhibitors help to maintain euglycemia in the body but do not cause hypoglycemia. Sulfonylureas, meglitinides, and to a lesser extent dipeptidyl peptidase (DPP)-IV inhibitors increase pancreatic insulin and may cause hypoglycemia following overdose. Although a single sulfonylurea tablet may produce symptomatic hypoglycemia in a toddler, noteworthy sequelae have not been reported. Larger overdoses are associated with significant morbidity and mortality in older children and adults.² Many oral anti-diabetic agents are prescribed in combination forms or in extended-release forms. History should include careful questioning to determine all active ingredients in the product as well as release form. Both biguanides and thiazolidinediones may be prescribed in adolescents for treatment of diabetes. Chronic toxicity seen with these agents includes lactic acidosis (biguanides) and hepatotoxicity (thiazolidinediones). A summary of the expected toxicity from each class of oral anti-diabetic drugs is found in Table 122-1.

SULFONYLUREAS

Pharmacology

Sulfonylureas stimulate pancreatic beta cells to release insulin³ (Fig. 122-1). Second-generation sulfonylureas (glimepiride, glipizide, and glyburide) are more commonly prescribed than the first generation (tolbutamide and chlorpromide). All of the second-generation agents are rapidly absorbed, have a duration of action of approximately 24 hours, and a single dose may produce mild symptomatic hypoglycemia in a young child.

Toxic Dose

Case reports, prospective case series, and a retrospective review document mild to moderate hypoglycemia following reported single-dose sulfonylurea ingestions.^4–6 There are no reports of deaths or permanent sequelae in young children after unintentional ingestion of these drugs.

Clinical Presentation

Signs and symptoms of hypoglycemia include dizziness, diaphoresis, anxiety, headache, confusion, fatigue, slurred speech, coma, and seizures. Delayed onset of toxicity has been reported, but this is seen in patients receiving parenteral dextrose administered to euglycemic patients with the intent of preventing hypoglycemia.

Management

Duration of observation of asymptomatic young children presenting with the history of sulfonylurea ingestion is problematic because of reports of delayed onset of hypoglycemia. Recommendations vary from 8–24 hours. Since delayed hypoglycemia occurred in children receiving prophylactic intravenous dextrose, this practice should be avoided. A 2005 literature review⁴ and a 1997 prospective multicenter observational series in 185 children⁷ both recommend 8 hours of observation. A 2011 retrospective medical record review of 93 children admitted to a single institution recommended 16 hours of observation.⁶ The median time for hypoglycemia was 4–5.5 hours, with the longest interval 13 hours. However, there was no mention of whether or not parenteral dextrose was administered.

Therefore, asymptomatic young children presenting with the history of sulfonylurea ingestion should not be treated with prophylactic intravenous dextrose. They should receive hourly point-of-care blood sugar measurements and may be discharged from the emergency department (ED) if 8 hours of euglycemia is documented.⁸

If the patient presents less than 1 hour after the ingestion of potentially toxic sulfonylurea, consider the administration of activated charcoal. If hypoglycemia occurs, administer an intravenous bolus of 0.5 g/kg of 25% dextrose followed by a 5% or 10% dextrose infusion. This often reverses the hypoglycemia of mild sulfonylurea poisoning. Unfortunately, dextrose is a secretagogue for sulfonylurea-sensitized beta cells resulting in insulin release. Thus hypoglycemia may be refractory to supplemental dextrose administration. Glucagon and corticosteroids, because of their hyperglycemic actions, may be considered for sulfonylurea-poisoned patients resistant to dextrose therapy. However, these interventions are ineffective because they also stimulate insulin secretion.