High insulin euglycaemia therapy

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Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Toxicological Indications

• Severe calcium channel blocker (CCB) poisoning with haemodynamic compromise.
• Severe beta-blocker poisoning with haemodynamic compromise.

Contraindications

• None.

Mechanism of Action

• Enhances myocardial inotropy by optimising metabolic conditions:
  • Increases lactate oxidation and eliminates myocardial fatty acid oxidation.
  • Improves intracellular glucose transport and vascular dilation without acting as a vasopressor.
• Glucose co-administration maintains euglycaemia during therapy.

Administration

Critical Care Protocol

• Only for critically ill patients under continuous monitoring.
• Initial Therapy:
  • IV bolus of 25 g glucose (50 mL of 50% solution).
  • IV bolus of short-acting insulin 1 IU/kg.
• Continuous Infusion:
  • Glucose infusion at 25 g/hour via central line, titrated to maintain euglycaemia.
  • Insulin infusion at 0.5 IU/kg/hour, increased to 1–2 IU/kg/hour or higher if needed.
• Therapy continues as long as cardiovascular instability persists.

Therapeutic Endpoints

• Wean therapy as cardiovascular toxicity resolves.

Adverse Drug Reactions and Management

Hypoglycaemia

• Titrate dextrose infusion to maintain euglycaemia.
• Bedside blood glucose levels (BGL):
  • Check every 10 minutes during initiation and titration.
  • Every 30–60 minutes once stable.

Electrolyte Imbalances

• Hypokalaemia:
  • Maintain serum potassium at 3.0–3.5 mmol/L.
  • Potassium shifts back extracellularly post-insulin withdrawal.
  • Check serum potassium hourly during initiation and every 6 hours when stable.
• Hypomagnesaemia and Hypophosphataemia:
  • Monitor and manage as needed.

Specific Considerations

• Pregnancy and Paediatrics: No restrictions on use.

Handy Tips

• Early initiation ensures better outcomes in severe CCB or beta-blocker toxicity.
• Peak inotropic response typically occurs within 1 hour of initiation.
• Glucose supplementation may be required for up to 24 hours post-HD discontinuation.

Pitfalls

• Delayed initiation in life-threatening CCB or beta-blocker toxicity.

Controversies

• Lack of human clinical trials directly comparing HDI with other treatments for CCB and beta-blocker toxicity.
• Aggressive protocols propose escalating insulin infusion to a maximum of 10 IU/kg/hour if no clinical improvement.
• Limited clinical experience with HDI for other toxin-induced shock states.