What are the indications and guidelines for high dose insulin (HDIT) therapy?

High Dose Insulin Therapy (HDIT): Indications and Guidelines

High dose insulin therapy (HDIT) is primarily indicated for calcium channel blocker and beta-blocker poisoning with documented myocardial dysfunction, where it serves as a first-line treatment to increase contractility and improve hemodynamics. 1

Primary Indications for HDIT

• HDIT is recommended as a first-line treatment for calcium channel blocker (CCB) poisoning with documented myocardial dysfunction (Grade 1D recommendation) 1
• HDIT is suggested for CCB poisoning even without documented myocardial dysfunction (Grade 2D recommendation) 1
• HDIT is recommended for severe beta-blocker toxicity causing hemodynamic compromise (Grade 1, Level B-NR) 2, 3
• HDIT is indicated for bradycardia and cardiac conduction delay associated with drug toxicity that is refractory to conventional treatments 1

Dosing Protocol

• Standard initial dosing for HDIT includes a bolus of 1 U/kg followed by an infusion of 1 U/kg/hr 1
• For refractory shock or periarrest conditions, incremental doses up to 10 U/kg/hr may be used if evidence of myocardial dysfunction is present 1
• Even without documented myocardial dysfunction, incremental doses up to 10 U/kg/hr may be considered in refractory shock (Grade 2D recommendation) 1
• Concurrent dextrose infusion is required to maintain euglycemia, with close monitoring of serum potassium 1

Mechanism of Action in Toxicology

• HDIT works through three main mechanisms: increased inotropy, increased intracellular glucose transport, and vascular dilatation 3
• HDIT functions as an inodilator rather than a true antidote, with a relatively slow onset of action (15-60 minutes) compared to catecholamine-based inotropes 4
• HDIT improves cardiac contractility in the setting of cardiogenic shock from CCB or beta-blocker poisoning 1
• HDIT has been shown to be superior to calcium salts, glucagon, epinephrine, and vasopressin in terms of survival in animal models of CCB and beta-blocker poisoning 3

Monitoring and Adverse Effects

• Major adverse effects include hypoglycemia and hypokalemia, requiring regular monitoring of glucose and electrolytes 3, 5
• Glucose supplementation will likely be required throughout therapy and for up to 24 hours after discontinuation of HDIT 3
• Potassium shifts from extracellular to intracellular space rather than decreasing total body stores 3
• Patients receiving extremely high dose insulin infusions (≥35 units/h) have higher rates of hypoglycemia (63% vs. 34%) compared to those with lower requirements 6

Treatment Algorithm for CCB/Beta-Blocker Poisoning

1. Initial assessment: Evaluate for signs of toxicity including hypotension, bradycardia, and cardiac dysfunction 1
2. First-line treatments:
   • Fluid resuscitation to correct vasodilation and low cardiac filling pressures 3
   • IV calcium to increase contractility and blood pressure (Grade 1D) 1
   • Vasopressors (norepinephrine for blood pressure, epinephrine for contractility and heart rate) 1
   • HDIT to increase contractility (Grade 1D) and blood pressure (Grade 2D) 1
3. For refractory cases:
   • Increase HDIT up to 10 U/kg/hr 1
   • Consider lipid emulsion therapy (Grade 1D-2D) 1
   • Consider VA-ECMO in centers where available (Grade 2D) 1

Special Considerations

• HDIT should be used concurrently with noradrenaline to counteract insulin-induced vasodilation 4
• HDIT has limited role in isolated vasoplegic shock where it may exacerbate toxicity 4
• Risk factors for hypoglycemia during insulin therapy include lower pretreatment blood glucose (<7 mmol/L), lower weight, renal insufficiency, older age, and nondiabetic status 5
• D10 solution running at 60 mL/hour provides 6 grams of carbohydrates per hour, which may be used for glucose supplementation during HDIT 7

Common Pitfalls to Avoid

• Delaying HDIT in favor of less effective conventional therapies in severe CCB or beta-blocker poisoning 3
• Using HDIT as first-line therapy for isolated vasoplegic shock 4
• Inadequate glucose monitoring and supplementation during HDIT 3, 5
• Failing to monitor for hypokalemia, which can persist beyond cessation of therapy 4
• Administering dextrose solutions too rapidly, which can cause hyperglycemia with adverse effects on the central nervous system 7