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    Patent Pending

    High-dose Insulin Euglycemia Therapy (HIET)

    Doses insulin for calcium-channel blocker or beta blocker overdose.
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    IMPORTANT

    This dosing tool is intended to assist with calculation, not to provide comprehensive or definitive drug information. Always double-check dosing of any drug and consult a pharmacist when necessary.

    INSTRUCTIONS

    Use in patients with cardiac drug-induced myocardial depression (cardiogenic shock).

    When to Use
    Pearls/Pitfalls
    Why Use
    • Cardiac induced myocardial depression from CCB toxicity (strongest evidence).
    • May also be used in cardiac induced myocardial depression from beta blocker toxicity.
    • Ultimate goal of HIET is improvement in organ perfusion.
    • Glucose, potassium, and ejection fraction should be monitored.
    • Most common adverse effects of HIET include hypoglycemia and hypokalemia.
    • Hypoglycemia may occur up to several hours after the insulin infusion has been completed.
    • Concentrate insulin infusion to prevent fluid overload.
    • Works by increasing myocardial glucose uptake, resulting in improved contractility.

    HIET should be considered concurrently with, or even prior to, initiation of vasopressors. HIET alone may improve the patient’s hemodynamic status, thus making vasopressors unnecessary and avoiding potential complications of vasopressor use.

    lbs
    mg/dL
    D50
    D25
    D10

    Result:

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    Next Steps
    Evidence
    Creator Insights

    Advice

    Give an initial insulin bolus to rapidly saturate insulin receptors to speed the physiological response.

    • 1 unit/kg bolus of regular human insulin along with 0.5 g/kg bolus of dextrose.
    • An infusion of regular insulin should immediately follow the bolus starting at 1 unit/kg/hr.

    If blood glucose is greater than 250 mg/dL (16.7 mmol/L), then the dextrose bolus is not necessary.

    Management

    • Assess cardiac function every 10 to 15 minutes after starting HIET.
    • If cardiac function remains depressed, then the insulin dose should be increased by 0.5-1 unit/kg increments.
    • Dosing recommendations typically range up to 10 units/kg/hr; however, doses up to 22 units/kg/hr have been used, and the maximum dose is not established. 
    • Typical duration of therapy has been 1 to 2 days, although HIET has been used for up to 4 days.

    Critical Actions

    • A continuous dextrose infusion, beginning at 0.5 g/kg/hr, should be concurrently initiated.
    • Dextrose can be started as D10, especially if central venous access not available, but it is ultimately best delivered as D25 or D50 via central venous access to lessen fluid overload.
    • Reduce the insulin infusion rate by 1 unit/kg/hr once the patient has stabilized, and reassess hourly for additional infusion reduction.
    • Reduction of insulin and dextrose may cause potassium shifting which should also be monitored.

    Formula

    Insulin bolus:

    • Intravenous bolus of regular insulin at a dose of 1 unit/kg.
    • If serum glucose <250 mg/dL, concurrently administer a bolus of dextrose 25-50 g (or 0.5-1 g/kg) IV.
      • Note: the calculator assumes D50 (50% dextrose in water) will be given for the initial bolus, and uses the weight-based dosing (0.5-1 g dextrose per kg patient weight; i.e., 1-2 cc D50 per kg patient weight).

    HIET continuous infusion:

    • Regular insulin: start 0.5–1 unit/kg/hr.
    • Dextrose: 0.5 g/kg/hr (titrate to maintain glucose 110–250 mg/dL).
    • If fluid overload is a concern, the insulin can be concentrated to 10 units/mL.
    • If hypoglycemia does occur, bolus with dextrose and/or increase dextrose infusion first before considering a decrease or cessation of insulin infusion.

    Continuous monitoring:

    • Serum glucose every 30 minutes for 1-2 hours until stable.
    • Potassium every 1 hour.

    Evidence Appraisal

    Most of the data comes from case series and animal/canine studies.

    Recent human case series include:

    Holger 2011

    • Aim: describe patient outcomes and adverse events of high dose insulin therapy in toxin induced cardiogenic shock.
    • Design: retrospective observational case series. 
    • Results:
      • n = 12 (5 beta blockers, 2 calcium channel blockers, 2 with combined beta blockers and calcium channel blockers, 1 tricyclic antidepressant, 2 polydrug).
      • Mean age 36.5 ± SD 11.7 years.
      • Mean maximum infusion rate: 8.35 units/kg/hr ±6.34.
      • Mean duration of infusion: 23.5 hr ±19.7.
      • Mean duration of glucose infusion post insulin: 25.2 hr ±17.7.
      • Survival: 11/12 patients. Patient who died expired after insulin was stopped (i.e., deviation from protocol).
      • Adverse events:
        • Hypoglycemia <60 mg/dL: 19 episodes of hypoglycemia in a total of 6 patients.
        • Hypokalemia <3 mEq/L: 8 patients.

    Greene 2007

    • Aim: examine clinical safety of HIET in CCB poisoning.
    • Design: prospective observational study, patients with cardiogenic shock secondary to CCB.
    • Results:
      • n = 7.
      • Mean age 54 years, range 37-75.
      • Maximum infusion rate 2 units/kg.
      • Survival: 6/7 patients.
      • Adverse events:
        • 3 patients who received 1 unit/kg insulin bolus had significant sustained rise in sBP >10 mmHg.
        • Hypoglycemia <65 mg/dL: 1 patient.
        • Hypokalemia <3.5 mEq/L: 1 patient.

    Literature

    Dr. Lewis Goldfrank

    About the Creator

    Lewis Goldfrank, MD, FACEP, FAAEM, FAACT, FACMT, FACP, is the Herbert W. Adams Professor of Emergency Medicine at New York University. He is also the medical director of the New York City Poison Control Center. Dr. Goldfrank is perhaps best known as author and editor of the primary toxicology reference Goldfrank's Toxicologic Emergencies.

    To view Dr. Lewis Goldfrank's publications, visit PubMed

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