Thanks to Dan Kim for giving a great talk (and to the audience of contributing lots of great learning points!) on a middle aged woman who presented with hypoglycemia after taking a dose of her sulfonylurea.
Recall that sulfonylureas work by inhibiting the ATP-sensitive potassium channel in pancreatic beta cells; this leads to increased endogenous insulin release. Long acting sulfonylureas (ie glyburide) are more likely than short-acting agents (glipizide, glimepiride) to cause hypoglycemia.
When thinking about hypoglycemia, it helps to think in terms of whether the patient is ill-looking or not
- drugs (insulin or insulin secretagogue, alcohol, ?others)
- Sepsis/critical illness
- Hormone deficiency (cortisol, glucagon or epinephrine)
- Endogenous hyperinsulinism
- post-gastric bypass hypoglycemia
- antibodies to insulin or insulin receptor
- Surreptitious/factitious hypoglycemia
Sulfonylurea toxicity is generally a clinical diagnosis based on history. There are sulfonylurea assays that can be sent, but they generally take too long to result and are thus of limited use
Management of sulfonylurea toxicity
- D5 or D10 gtt
- should not be used as monotherapy for sulfonylurea toxicity, as it will cause transient hyperglycemia that triggers insulin release and further episodes of hypoglycemia
- works by decreasing insulin release from beta cells
- Give for the first 24h, and then stop; can restart if hypoglycemia recurs
- NB: very short acting, so should only be used as a temporizing measure while getting IV access or some other longer-acting source of glucose
Activated charcoal can be used within 2-3h of the ingestion, but hemodialysis has not been shown to be effective. Diazoxide, an older drug which also inhibits pancreatic insulin release, used to be used, but is less effective than octreotide and can cause hypotension.
We talked briefly about the threshold effect with loop diuretics:
Lastly, this study compared bolus vs continuous infusion of lasix in patients with ADHF, and found that there was no real difference between the two dosing strategies. However, keep in mind that this was part of a research setting, where even bolus doses were probably timed perfectly. In real life, doses may be given late (ie beyond the point that the previous dose is effective), so continuous diuretic infusion may still have a role in clinical practice.
- Oh S et al. Loop Diuretics In Clinical Practice. Electrolyte Blood Press 2015.
- Felker et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. NEJM 2011.
- Brater DC, Day B, Burdette A, et al. Kidney Int 1984; 26:183.