Canadian antidote guide

Insulin Regular

• Humulin R™
• Novolin ge Toronto™

• Severe cardiovascular toxicity (hypotension, systemic hypoperfusion) in cases of:
  • Poisoning by Calcium Channel Blockers.
  • Poisoning by Beta-Blockers
  • Poisoning by Co-Ingestion of Beta-Blockers and Calcium Channel Blockers.

• Hypoglycemia
• Hypokalemia

• Vital signs
• Capillary glucose every 30 min (maintain glucose above 5.5 mmol/L)
• Serum potassium every 2 hours (maintain around 3.0 mmol/L)
• Fluid balance
• State of consciousness

• Improved hemodynamic state that allows the gradual withdrawal of sympathomimetic amines.
• Average length of treatment is often longer than 24 h.
• Dextrose may need to be continued for an additional 24 h after the discontinuation of insulin.
  • Some examples of how to wean an insulin infusion are presented below:
    • For calcium channel blockers poisonings:
      • If the patient is stabilized, and the peak of toxicity appears to be over and the blood glucose has decreased to approximately 16 mmol / L or less (if the patient was hyperglycemic) then,
      • Decrease the insulin infusion by 0.5 to 1 U/kg/h every hour, but try to keep at least 0.5 to 1 U/kg/h until all the vasopressors/inotropes are weaned (unless the vasopressors/inotropes requirement can be explained by a cause other than the calcium channel blocker poisoning).
      • Increase again the insulin infusion if the vasopressors/inotropes requirements increase following the weaning attempt of the insulin infusion.
    • For beta-blockers poisonings:
      • If the patient is stabilized and the peak toxicity appears to be over,
      • Decrease the insulin infusion by 0.5 to 1 U/kg/h every hour, but try to keep at least 0.5 to 1 U/kg/h until all the vasopressors/inotropes are weaned (unless the vasopressors/inotropes requirement can be explained by a cause other than the beta-blocker poisoning).
      • Increase again the insulin infusion if the vasopressors/inotropes requirements increase following the weaning attempt of the insulin infusion.

Intravenous Route (IV)

• Direct IV
  • Administer loading dose by direct IV over 1 min.
  • To facilitate administration of small doses (e.g., pediatric doses), dilute with NS.
  • Administer using a volumetric pump.
• Continuous IV infusion:
  • Administer using a volumetric pump.
  • Due to the adsorption of insulin into PVC material (bags, tubes), the actual quantity of bio-available insulin is slightly lower than the quantity prepared. Consequently, infusion rate adjustments must be based on observed clinical effect rather than on the prepared insulin dose.
  • Before connecting, flush out the first 10 - 20 ml of the solution (to avoid adsorption of insulin into PVC).
  • Standard Preparation: Final concentration of 1 unit/ml.
    • 100 units (1 ml) in 99 ml of NS or D5W. Final volume = 100 ml. Final concentration = 1 unit/ml.
    • 250 units (2.5 ml) In 247.5 ml of NS or D5W. Final volume of 250 ml. Final concentration = 1 unit/ml.
  • Concentrated Preparation: Final concentration of 16 units/ml
    • When administering high doses of insulin (e.g., 2 - 10 units/kg/h) or during fluid restriction:
    • WARNING: This concentration is generally not programmed in “smart” volumetric pumps.
    • 4000 units (40 ml) in 210 ml of NS. Final volume = 250 ml. Final concentration = 16 units/ml.
    • 8000 units (80 ml) in 420 ml of NS. Final volume = 500 ml. Final concentration = 16 units/ml.

Subcutaneous Route (SC)

• IV or IO routes are the preferred routes.

Intramuscular Route (IM)

• IV or IO routes are the preferred routes.

Intraosseous Route (IO)

• Possible alternative to IV route.

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

• Compatible solutions: NS, D5W, D10W, D5W+½NS, D5W+¼NS, LR.
• Y-site compatibility: aminophylline, atropine, benztropine, bicarbonate (sodium), dexamethasone, esmolol, fentanyl, folic acid, hydrocortisone, hydromorphone, leucovorin calcium, lidocaine, lorazepam, magnesium (sulfate), mannitol, meperidine, methylprednisolone, metoclopramide, metoprolol, milrinone, naloxone, nitroglycerin, sodium nitroprusside, octreotide, pancuronium, phenobarbital, phytonadione (vitamin K1), potassium (acetate and chloride), procainamide, promethazine, propofol, pyridoxine, remifentanyl, sufentanil, thiamin, verapamil.
• Y-site incompatibility: chlorpromazine, dantrolene, diazepam, diphenhydramine, isoproterenol, ketamine, labetalol, phentolamine, phenylephrine, phenytoin, prochlorperazine, propranolol, protamine, rocuronium.

Stability

• Insulin vials and cartridges must be stored in the refrigerator (2°C to 8°C).
• Insulin vials and cartridges that have been opened or stored at room temperature should be discarded after 28 days.
• Glass, PVC and plastic surfaces adsorb insulin. Adsorption level depends on several factors, such as temperature, length of contact and concentration of the solution. The final concentration of solutions for continuous IV infusion may vary. Flush the tube with insulin solution before administration to saturate the connection sites in the tubing, thus improving the accuracy of the administered dose.
• Solutions administered by continuous IV infusion are considered to have a stability of 24 h.
• Concentrated 16 units/ml of insulin solution in a PVC bag of NS will be stable for 14 days at room temperature or in the refrigerator.

• Novolin ge Toronto, 100 units/ml, Inj. Sol., 10 ml vial or 3 ml cartridge, Novo Nordisk Canada Inc, DIN 02024233 and 02024284, 
• Humulin R, 100 units/ml, Inj. Sol., 10 ml vial or 3 ml cartridge, Eli Lilly Canada, DIN 00586714 and 01959220, 
•  

• At least 2,000 units.

Engebretsen, Kristin. 2016. “Euglycemic Insulin Therapy.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 1–10. Springer International Publishing.



Engebretsen, Kristin M., Kathleen M. Kaczmarek, Jenifer Morgan, and Joel S. Holger. 2011. “High-Dose Insulin Therapy in Beta-Blocker and Calcium Channel-Blocker Poisoning.” Clinical Toxicology 49 (4):277–83.



Laskey, Dayne, Rajesh Vadlapatla, and Katherine Hart. 2016. “Stability of High-Dose Insulin in Normal Saline Bags for Treatment of Calcium Channel Blocker and Beta Blocker Overdose.” Clinical Toxicology 54 (9):829–32.



Page, Colin B., Nicole M. Ryan, and Geoffrey K. Isbister. 2017. “The Safety of High-Dose Insulin Euglycaemia Therapy in Toxin-Induced Cardiac Toxicity.” Clinical Toxicology , October, 1–8.



St-Onge, M., P-A Dubé, S. Gosselin, C. Guimont, J. Godwin, P. M. Archambault, J-M Chauny, et al. 2014. “Treatment for Calcium Channel Blocker Poisoning: A Systematic Review.” Clinical Toxicology 52 (9):926–44.



St-Onge, Maude, Kurt Anseeuw, Frank Lee Cantrell, Ian C. Gilchrist, Philippe Hantson, Benoit Bailey, Valéry Lavergne, et al. 2017. “Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults.” Critical Care Medicine 45 (3):e306–15.



Zuckerman, Matthew, Howard A. Greller, and Kavita M. Babu. 2015. “A Review of the Toxicologic Implications of Obesity.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 11 (3):342–54.