Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose

Clin Toxicol (Phila). 2016 Nov;54(9):829-832. doi: 10.1080/15563650.2016.1209766. Epub 2016 Jul 19.


Context: High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available.

Objective: To determine the stability of insulin at 16 units/mL in 0.9% saline solution.

Materials and methods: Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days.

Results: Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days.

Discussion: Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid.

Conclusion: Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.

Keywords: Insulin; beta blocker; calcium channel blocker; hyperinsulinemia euglycemia; stability.

MeSH terms

  • Adrenergic beta-Antagonists / poisoning*
  • Calcium Channel Blockers / poisoning*
  • Drug Overdose
  • Drug Packaging
  • Drug Stability
  • Drug Storage
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry*
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / chemistry*
  • Polyvinyl Chloride / chemistry
  • Refrigeration
  • Sodium Chloride / chemistry
  • Temperature
  • Time Factors


  • Adrenergic beta-Antagonists
  • Calcium Channel Blockers
  • Hypoglycemic Agents
  • Insulin
  • Sodium Chloride
  • Polyvinyl Chloride