A suicide attempt, or something else?

The authors’ observations

In the context of Ms. A’s prior suicide attempt and history of self-harm, the pediatric team was concerned that her presentation was consistent with a suicide attempt and consulted the psychiatry service.

Glipizide is a second-generation sulfonylurea used to treat type 2 diabetes. It lowers blood glucose by stimulating pancreatic insulin secretion. It is a rare drug of overdose.¹ Although pediatric glipizide overdoses have been documented, there are currently no pediatric or adolescent glipizide pharmacokinetic studies in the literature.^1-4 In adults, the immediate-release formulation has 100% oral bioavailability, with a maximum plasma concentration (T_max) of approximately 2 hours.⁵ The half-life typically ranges from 4 to 6 hours in adults.⁶ Patients who do not have diabetes are much more susceptible to the hypoglycemic effects of glipizide because the medication simulates their fully functional pancreas to produce a vigorous insulin response.

Ms. A’s significantly elevated insulin was consistent with normal glipizide effects in a healthy child, while the elevated C-peptide was consistent with insulin being endogenously produced, which ruled out ingestion of her parent’s insulin. Importantly, the pediatric endocrinology team noted that, in their experience, a single 5- to 10-mg dose of glipizide IR was sufficient to lower blood glucose levels to the low 30s mg/dL in the context of a functional pancreas, which suggested that Ms. A might have accidentally ingested a single glipizide IR tablet, and might be telling the truth when she denies deliberately ingesting it to hurt herself.

The clinical value of pharmacokinetics

The screen of Ms. A’s toxicology sample detected glipizide. The laboratory used a semi-quantitative serum screen of several hypoglycemic agents. A positive result for each agent is based on a quantitative cut-off value, which is 3 ng/mL for glipizide. The clinical chemist on call was asked to assist in interpreting the results. The serum specimen collected on Day 1 had a significantly positive glipizide result of 86 to 130 ng/mL. The maximum effective glipizide concentration for adult patients with diabetes is 100 ng/mL.⁷ Thus, the glipizide level of 86 to 130 ng/mL (20.5 hours after initial symptoms) is consistent with the clinical presentation of persistent hypoglycemia requiring ongoing glucose replacement therapy.

Due to the lack of pediatric pharmacokinetic data for glipizide and only a single serum measurement, it is not possible to estimate the glipizide concentration at the time of maximal symptoms (loss of consciousness at 2:30 pm followed by a seizure on the day of presentation to the ED). In a prospective study of glipizide dose and hypoglycemia (blood glucose <60 mg/dL) in pediatric ingestion cases, a dose range of glipizide 0.05 to 0.58 mg/kg was reported to predict pediatric hypoglycemia with 95% confidence (N = 67, P < .005).¹ Because Ms. A weighed 51 kg, ingestion of a single glipizide IR 10-mg tablet (0.2 mg/kg) could induce hypoglycemia. If the 2-hour T_max and 4- to 6-hour half-life reported for adults held true for Ms. A, a glipizide result of 86 to 130 ng/mL back-calculated to a serum glipizide of >1,000 ng/mL at the time she was discovered unconscious. This could be consistent with ingestion of at least 1 glipizide IR 10-mg tablet between 12:30 to 2:30 pm on the day before Ms. A was brought to the ED. This account would corroborate Ms. A’s recollection of taking a single pill of what she thought was her montelukast. If only a single pill had been ingested, that also could explain why her parents had not noticed any tablets missing.

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