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Introduction

  1. Pharmacology. Epinephrine is an endogenous catecholamine that is used primarily in emergency situations to treat anaphylaxis or cardiac arrest. Epinephrine stimulates all adrenergic receptors (alpha1, alpha2, beta1, beta2, and beta3) resulting in smooth muscle relaxation of the bronchial tree, increased peripheral vascular resistance via alpha1-mediated vasoconstriction, and cardiac stimulation via beta1. Additional beneficial effects include inhibition of histamine release from mast cells and basophils. Epinephrine is not active after oral administration. Subcutaneous injection produces effects within 5-10 minutes, with peak effects at 20 minutes. Intravenous or inhaled administration produces much more rapid onset. Epinephrine is inactivated rapidly in the body, with an elimination half-life of 2 minutes.
  2. Indications
    1. Anaphylaxis and anaphylactoid reactions.
    2. Occasionally used for hypotension resulting from overdose with beta-blockers, calcium antagonists, and other cardiac-depressant drugs.
    3. Asystole/pulseless arrest, pulseless ventricular tachycardia/ventricular fibrillation.
    4. Management of hypotensive shock.
    5. Symptomatic bradycardia unresponsive to atropine or pacing.
  3. Contraindications. There are no absolute contraindications in a life-threatening situation. Epinephrine is relatively contraindicated in patients with heart disease, peripheral arterial occlusive vascular disease with thrombosis, ergot poisoning, narrow-angle glaucoma, general anesthesia with halogenated hydrocarbons, and in situations in which vasopressors may be contraindicated such as thyrotoxicosis.
  4. Adverse effects
    1. Anxiety, restlessness, tremor, and headache.
    2. Severe hypertension, which may result in intracranial hemorrhage, pulmonary edema, or myocardial necrosis or infarction.
    3. Other cardiovascular effects such as chest pain, palpitations, tachycardia, ectopy, and ventricular dysrhythmias.
    4. Use with caution in patients intoxicated by halogenated or aromatic hydrocarbon solvents and anesthetics because these agents may sensitize the myocardium to the arrhythmogenic effects of epinephrine.
    5. Tissue necrosis after extravasation or intra-arterial injection. Note: Accidental discharge of an auto-injector rarely causes serious injury.
    6. Aggravation of tissue ischemia, resulting in gangrene.
    7. Anaphylactoid reaction, which may occur owing to the bisulfite preservative in patients with sulfite hypersensitivity.
    8. Hypokalemia, hypophosphatemia, hyperglycemia, and leukocytosis may occur owing to the beta-adrenergic effects of epinephrine.
    9. Use in pregnancy. FDA Category C (indeterminate). Epinephrine is teratogenic in animals, crosses the placenta, can cause placental ischemia, and may suppress uterine contractions, but these effects do not preclude its acute, short-term use for a seriously symptomatic patient (Introduction).
  5. Drug or laboratory interactions
    1. An enhanced arrhythmogenic effect may occur when epinephrine is given to patients with chloral hydrate overdose or anesthetized with halogenated general anesthetics.
    2. Use in patients taking propranolol and other nonselective beta-blockers may produce severe hypertension owing to blockade of beta2-mediated vasodilation, resulting in unopposed alpha-mediated vasoconstriction.
    3. Cocaine and cyclic antidepressants may enhance stimulant effects owing to inhibition of neuronal epinephrine reuptake.
    4. Monoamine oxidase inhibitors may enhance pressor effects because of decreased neuronal epinephrine metabolism.
    5. Digitalis intoxication may enhance the arrhythmogenicity of epinephrine.
  6. Dosage and method of administration
    1. Caution: Avoid extravasation. The intravenous infusion must be free-flowing, and the infused vein should be observed frequently for signs of subcutaneous infiltration (pallor, coldness, or induration).
      1. If extravasation occurs, stop infusion immediately, disconnect the line, and elevate the extremity. Consider infiltrating the affected area with phentolamine, 5-10 mg diluted in 10-15 mL of normal saline (children: 0.1-0.2 mg/kg; maximum, 10 mg total) via a fine (25-27-gauge) hypodermic needle; improvement is evidenced by hyperemia and return to normal temperature.
      2. Alternatives to phentolamine:
        1. Topical application of nitroglycerin 2% paste/ointment: apply a 1-inch strip to site of ischemia (may be repeated every 8 hours as necessary).
        2. Terbutaline: Infiltrate site with 1 mg terbutaline diluted in 1 mL normal saline.
    2. Mild-to-moderate allergic reaction. Give 0.3-0.5 mg IM (children: 0.01 mg/kg; maximum, 0.5 mg). May be repeated after 5-15 minutes if needed.
    3. Severe anaphylaxis. Give 0.05-0.1 mg IV every 5-10 minutes (children: 0.01 mg/kg; maximum, 0.1 mg) or an IV infusion at 1-4 mcg/min. If intravenous access is not available, the endotracheal route may be used; give 0.5 mg (5 mL of the 0.1-mg/mL solution) down the endotracheal tube.
    4. Hypotension. Infuse at 0.01-0.5 mcg/kg/min; titrate upward every 5 minutes as necessary. If the patient has refractory hypotension and is on a beta-adrenergic-blocking drug, consider glucagon.