1-844-764-7669 Health Care Professionals: 1 (902) 470-8161
Poisoning Information for the Public & Health Care Professionals

Atlantic Canada Poison Centre
Antidote Kit Manual

1-800-565-8161 or 902-470-8161 | atlanticcanadapoisoncentre.ca
Last updated: 02/2022
Pediatric Adult
Last updated: 02/2022
Antidote
Pediatric

Insulin-Regular

HumuLIN-R, NovoLin ge Toronto

Print Monograph
Antidote
Pediatric

Insulin-Regular

HumuLIN-R, NovoLin ge Toronto

ALERT: Refer to Dextrose monograph for concurrent administration

Indications

  • Hypotension due to calcium channel blocker toxicity or beta blocker toxicity.

Dosage

Administer initial dose followed immediately by infusion. 

Concurrent dextrose is required

Initial dose:

  • 1 unit/kg IV direct

Continuous Infusion:

  • Start at 1 unit/kg/hour 

- Titrate by 1 unit/kg/hour every 30 minutes up to 10 units/kg/hour to achieve goals of therapy: adequate perfusion evidenced by MAP 60 to 65 mmHg, urine output greater than 0.5 mL/kg/hour, stable or decreasing lactate.

- More aggressive titration may be required for some patients. 

- Contact the Atlantic Canada Poison Centre for more guidance and refer to “administration” section for details.

SAMPLE CALCULATION FOR A 12 KG PERSON:

- IV direct dose:
     1 unit/kg x 12 kg = 12 units (0.12 mL of regular insulin 100 units/mL)
 

- IV infusion dose:
     1 unit/kg/hour x 12 kg = 12 units/hour
 

Administration

ONLY REGULAR INSULIN MAY BE ADMINISTERED IV. Ensure you are using the correct product.

IV Direct: Dose may be administered undiluted over 1 minute. Dilution in 10 mL sodium chloride 0.9% or dextrose 5% in water may be used to facilitate administration of small volumes.

Continuous Infusion
For a final concentration of 16 units/mL:

  • 50 mL syringe: Add 8 mL (800 units) of regular insulin 100 units/mL to 42 mL sodium chloride 0.9%. Total volume 50 mL
  • 250 mL bag:  Add 40 mL (4000 units) of regular insulin 100 units/mL to 210 mL sodium chloride 0.9%. Total volume 250 mL 

IMPORTANT MONITORING INFORMATION:

  • Blood glucose should be monitored every 30 minutes for the first hour of therapy AND until stable AND after any dosage adjustment. After the initial hour of monitoring and stabilization of blood glucose, hourly monitoring is required. Therapeutic goal is to maintain blood glucose 6 - 14 mmol/L. Desired glucose levels should be specified.
  • Monitor blood glucose concentrations for a minimum of 6 hours and up to 24 hours after the infusion is discontinued. Late onset hypoglycemia has been reported.
  • Monitor serum potassium hourly. If potassium is less than 2.8 mmol/L, administer supplemental potassium to maintain a level between 2.8 - 3.2 mmol/L. Mild hypokalemia may augment myocardial cell function by improving calcium entry into cells and increasing the effect of insulin.
  • Monitor serum sodium hourly. In the pediatric population hyponatremia is a concern so requires close monitoring.
  • Therapeutic goal is improved organ perfusion, manifested by improved blood pressure, mental status and urine output; in addition, reversal of acidemia and decreasing lactate may be markers of improved perfusion.
  • If the patient is stabilized and the peak toxicity appears to be over, infusions may be decreased by 1 unit/kg/h every 30 to 60 minutes.  Try to keep insulin at least 1 unit/kg/h until all vasopressors / inotropes are weaned.  Patient should be monitored for recurrence of hemodynamic instability during the weaning process.  Increase the insulin infusion again if the vasopressor / inotrope requirements increase following the weaning attempt of the insulin infusion.

Compatibility, Stability

  • Vials should be stored in refrigerator.
  • Insulin solution of 16 units/mL should be prepared in sodium chloride 0.9%.  Insulin 16 units/mL in sodium chloride 0.9% in PVC bag stable for 24 hours at room temperature. 
  • Insulin infusions adsorb to glass, PVC and plastic surfaces. The degree of adsorption depends on many factors such as concentration of the solution, contact time with adsorbing surfaces and temperature. Potency may vary. Flushing the tubing prior to patient administration may saturate the binding sites in the tubing and improve the accuracy of the dose administered.

Potential Hazards of Administration

  • Hypoglycemia
  • Hypokalemia, Hyponatremia
  • Hypomagnesemia, hypophosphatemia
  • Nausea

Azendour, H., Belyamani, L., Atmani, M., Balkhi, H., & Haimeur, C. (2010). Severe amlodipine intoxication treated by hyperinsulinemia euglycemia therapy. The Journal of Emergency Medicine, 38(1), 33.

Bailey, B., Blais, R., Gaudreault, P., Gosselin, S., & Laliberte, M. (2009). Antidotes en toxicologie d'urgence (3rd ed.). Quebec, Canada: Centre antipoison du Quebec.

Doepker, B., Healy, W., Cortez, E., & Adkins, E. J. (2014). High-dose insulin and intravenous lipid emulsion therapy for cardiogenic shock by intentional calcium-channel blocker and beta-blocker overdose: A case series. The Journal of Emergency Medicine, 46(4), 486-490.

Holger, J. S., Stellplug, S. J., Cole, J. B., Harris, C. R., & Engebretsen, K. M. (2011). High-dose insulin: A consecutive case series in toxin-induced cardiogenic shock. Clinical Toxicology (Philadelphia, Pa.), 49, 653-658.

IWK Regional Poison Centre. (2011). Beta-adrenergic antagonists (beta-blockers): A brief overview for emergency departments. Unpublished manuscript.

IWK Regional Poison Centre. (2011). Calcium channel blockers: A brief overview for emergency departments. Unpublished manuscript.

Micromedex, T. H. A. (2014). Micromedex health care systems. Retrieved from http://www.micromedexsolutions.com

Olson, K. R. (2007). Poisoning & drug overdose (Sixth ed.). New York: McGraw Hill.

Page, C. B., Hacket, L. P., & Isbister, G. K. (2009). The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: A case report. Journal of Medical Toxicology, 5(3), 139.

Patel, N. P., Pugh, M. E., & Goldburg, S. (2007). Hyperinsulinemic euglycemia therapy for verapamil poisoning: A review. American Journal of Critical Care, 16, 498-503.

Phelps SJ, C. C. (2013).  Teddy bear, pediatric injectable drugs. Retrieved from http://www.pharmpress.com/product/MC_PED/pediatric-injectable-drugs

Shannon, M. W., Borron, S. W., & Burns, M. J. (2007). Haddad and Winchester's clinical management of poisoning and drug overdose (Fourth ed.). Philadelphia: Saunders Elsevier.

Smollin, C. G. (2010). Toxicology: Pearls and pitfalls in the use of antidotes. Emergency Medicine Clinic of North America, 28, 149-161.

Trissel, Lawrence, A,. (2013). Handbook on injectable drugs (17th ed.). Bethesda, Maryland: American Society of Health-System Pharmacists

Yuan, T. H., Kerns, I. W. P., & Tomaszewski. (1999). Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol, 37, 463.