Isoproterenol

Aka: Isoproterenol, Isuprel

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II. Indications

  1. Other inotropic agents (Dobutamine, Amrinone) are preferred over Isoproterenol
  2. Refractory and hemodynamically significant, Symptomatic Bradycardia (pulse present)
    1. Specific Uses
      1. Heart Block
      2. Bradycardia in denervated transplanted heart
    2. Unresponsive to other measures
      1. Atropine
      2. Epinephrine
      3. Transcutaneous Pacing or transvenous pacing
      4. Dopamine

III. Contraindications

  1. Ischemic Heart Disease

IV. Precautions

  1. Decreases Diastolic Blood Pressure
    1. No alpha adrenergic effect
    2. Increases Heart Rate (less diastolic filling time)
  2. May precipitate Myocardial Ischemia
    1. Increases myocardial oxygen demand
    2. Decreases coronary perfusion
  3. Induces Arrhythmias
    1. Ventricular Tachycardia
    2. Ventricular Fibrillation
  4. Exacerbates tachyarrhythmias due to Digitalis Toxicity
  5. Precipitates Hypokalemia

V. Dosing: Pediatric Infusion (Same as Epinephrine preparation)

  1. Preparation
    1. Draw up "x" mg of Isoproterenol
    2. Where "x" = 0.6 x Weight in Kilograms
    3. Add enough D5W or NS for 100 ml total
    4. At this dilution:
      1. Infusion rate of 1 ml/h provides 0.1 ug/kg/min
  2. Start Dose: 10 ml/hour (10 ug/kg/min)
  3. Titrate to clinical response, adjusting every 5 min

VI. Mechanism

  1. Synthetic Sympathomimetic amine
  2. Pure Beta Adrenergic Agonist
    1. Potent Chronotropic effects (b1)
      1. Increases Heart Rate (more than Epinephrine)
      2. Potentiates AV conduction
    2. Potent Inotropic effects (b1)
      1. Increases cardiac contractility
      2. Markedly increases Cardiac Output
    3. Potent peripheral vasodilatation (b2)
      1. Decreases Diastolic pressure and mean arterial pressure
    4. Bronchodilation (b2)
    5. Endocrine
      1. Increased Serum Glucose via glycogenolysis and Gluconeogenesis (b2)
      2. Increased fat breakdown via lipolysis of Triglycerides (b1)
    6. Other
      1. Decreased intestinal tone and motility
      2. Decreases Mast Cell release
  3. Markedly increases myocardial oxygen demand (b1)
    1. May provoke Myocardial Ischemia
    2. May decrease coronary perfusion

VII. Pharmacokinetics

  1. Very short Half-Life (<1.5 minutes)
    1. As with other Catecholamines, rapid metabolism by COMT (but minimal metabolism by MAO)

VIII. Dosing

  1. Preparation
    1. Dissolve 1 mg Isoproterenol in 250 ml D5W (4 mcg/ml, 75 ml/h = 5 mcg/min) OR
    2. Dissolve 2 mg Isoproterenol in 250 ml D5W (8 mcg/ml, 37.5 ml/h = 5 mcg/min)
  2. Adult Infusion
    1. Start Dose: 2 mcg/min IV
    2. Titrate: 2-10 mcg/min to clinical response
      1. Target Heart Rate over 60 beats per minute
    3. Maximum: 20 mcg/min
  3. Pediatric Infusion
    1. Start Dose: 0.05 mcg/kg/min IV
    2. Titrate: Increase by 0.1 mcg/kg/min every 5 to 10 minutes to clinical response
      1. Target Heart Rate over 60 beats per minute
    3. Maximum: 2 mcg/kg/min up to 20 mcg/min (or signs of toxicity)

IX. Safety

  1. Unknown safety in Lactation
  2. Pregnancy Category C

X. Resources

  1. Isoproterenol Injection Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f80ce132-1570-43bf-b4a6-0ffbdea5d218
  2. Isoproterenol (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK526042/

XI. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Olson (2020) Clinical Pharmacology, Medmasters, Miami, p. 13-33
  3. Goldstein (2010) Clin Auton Res 20(6):331-52 +PMID: 20623313 [PubMed]

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