Epinephrine

Indications

Advanced Cardiac Life Support (ACLS) (see Advanced Cardiac Life Support, [[Advanced Cardiac Life Support]])

  • Indications
    • Asystole (see Asystole, [[Asystole]])
    • Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]]): symptomatic and unresponsive to atropine or pacing
    • Pulseless Electrical Activity (PEA)
    • Pulseless Ventricular Tachycardia (VT) (see Ventricular Tachycardia, [[Ventricular Tachycardia]])
    • Ventricular Fibrillation (VF) (see Ventricular Fibrillation, [[Ventricular Fibrillation]])

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

  • Clinical Efficacy

Asthma (see Asthma, [[Asthma]])

  • Subcutaneous Use in the Setting of Status Asthmaticus is No Longer Recommended

Hemoptysis During Bronchoscopy (see Hemoptysis, [[Hemoptysis]] and Bronchoscopy, [[Bronchoscopy]])

  • Clinical Efficacy

Maintenance of Mydriasis During Ocular Surgery

  • May Be Used for this Indication

Post-Extubation Laryngeal Edema/Stridor (see Stridor, [[Stridor]])

  • Rationale: results in local vasoconstriction, decreasing laryngeal edema
  • Clinical Efficacy: efficacy is unclear
    • Pediatric Trial of Dexamthasone and Nebulized Epinephrine in Laryngeal Edema (Int J Pediatr Otorhinolaryngol, 2009) [MEDLINE]: dexamethasone and L-epinephrine did not reduce the clinical progression of airway obstruction due to laryngeal edema in the early post-extubation period

Septic Shock/Hypotension (see Sepsis, [[Sepsis]] and Hypotension, [[Hypotension]])

  • Clinical Efficacy

Pharmacology

Pharmacologic Effects at Adrenergic Receptors

  • α1-Adrenergic Receptor Agonist (see α1-Adrenergic Receptor Agonists, [[α1-Adrenergic Receptor Agonists]])
    • Vascular Smooth Muscle α1-Adrenergic Receptors
      • Mediate Vasoconstriction
  • β1-Adrenergic Receptor Agonist (see β1-Adrenergic Receptor Agonists, [[β1-Adrenergic Receptor Agonists]])
    • Cardiac β1-Adrenergic Receptors
      • Mediate Increased Atrioventricular Nodal Conduction Velocity
      • Mediate Increased Chronotropy
      • Mediate Increased Inotropy
    • Renal Juxtaglomerular Cell β1-Adrenergic Receptors
      • Mediate Increased Renin Release
  • β2-Adrenergic Receptor Agonist (see β2-Adrenergic Receptor Agonists, [[β2-Adrenergic Receptor Agonists]])
    • Bronchial Smooth Muscle β2-Adrenergic Receptors
      • Mediate Bronchodilation
    • Gastrointestinal β2-Adrenergic Receptors
      • Mediate Slowing of Peristalsis
      • Mediate Slowing of Secretions
    • Hepatic β2-Adrenergic Receptors
      • Mediate Gluconeogenesis
      • Mediate Glycogenolysis
      • Mediate Lipolysis
    • Ocular Ciliary Muscle β2-Adrenergic Receptors
      • Mediate Flow of Aqueous Humor
      • Mediate Accommodation
    • Uterine Muscle β2-Adrenergic Receptors
      • Mediate Uterine Relaxation (Tocolysis)
    • Urinary Bladder Detrusor Muscle β2-Adrenergic Receptors
      • Mediate Detrusor Muscle Relaxation
    • Vascular Smooth Muscle β2-Adrenergic Receptors
      • Mediate Vasodilation
  • β3-Adrenergic Receptor Agonist
    • Adipose Tissue β3-Adrenergic Receptors
      • Mediate Lipolysis

Pharmacokinetics

  • Half-Life: <5 min
  • Distribution: epinephrine does not cross the blood-brain barrier

Metabolism

  • Hepatic Metabolism of Circulating Epinephrine
    • Urinary Excretion of Inactive Metabolites, Metanephrine, Sulfate and Hydroxy Derivatives of Mandelic Acid, and Small Amounts of Unchanged Drug
  • Uptake by Adrenergic Neurons and Metabolism by Monoamine Oxidase (MAO) and Catechol-0-Methyltransferase

Administration

Advanced Cardiac Life Support (ACLS) (see Advanced Cardiac Life Support, [[Advanced Cardiac Life Support]])

Asystole/Pulseless Electrical Activity (PEA)/Pulseless Ventricular Tachycardia (VT)/Ventricular Fibrillation

  • Intravenous (IV): 1 mg (1:10,000 Dilution = 0.1 mg/mL) q3-5 min
  • Intraosseous (IO): 1 mg (1:10,000 Dilution = 0.1 mg/mL)
  • Intratracheal (via Endotracheal Tube): 2-2.5 mg in 10 ml normal saline (1:10,000 Dilution = 0.1 mg/mL) q3-5 min
    • May Cause False-Negative Readings with Exhaled Carbon Dioxide (CO2) Detectors

Symptomatic Bradycardia (Unresponsive to Atropine and/or Pacing)

  • Intravenous (IV) Infusion: 2-10 μg/min

Septic Shock/Hypotension (see Sepsis, [[Sepsis]] and Hypotension, [[Hypotension]])

  • Intravenous (IV) Infusion: 2-10 μg/min

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

  • Intramuscular (IM) (see Anaphylaxis, [[Anaphylaxis]]): 0.3 mg (1:1,000 Dilution = 1 mg/mL) into anterior middle third of the thigh
    • Same Dose as Preloaded Epinephrine Injector Devices (EpiPen, Adrenaclick, Auvi-Q)
  • Intravenous (IV): recommended only for patients with refractory hypotension and lack of response to multiple intramuscular epinephrine injections or if patient is in cardiopulmonary arrest
  • Subcutaneous (SQ): no longer recommended (due to slower and less reliable absorption than intramuscular administration)

Post-Extubation Laryngeal Edema/Stridor (see Stridor, [[Stridor]])

  • Nebulized Racemic Epinephrine: 1 mg in 5 mL of normal saline

Hemoptysis During Bronchoscopy (see Hemoptysis, [[Hemoptysis]] and Bronchoscopy, [[Bronchoscopy]])

  • Intrabronchial (Topical Instillation via Bronchoscope)
    • Dilute 10 mL of 1:10,000 Epinephrine (0.1 mg/mL) + 10 mL Normal Saline: yields 20 mL of 1:20,000 Epinephrine
    • Instill 2 mL Intrabronchially (Via Bronchoscope) at a Time (Max Total Dose: 10 mL = 0.5 mg)

Dose Adjustment

  • Hepatic: none
  • Renal: none

Extravasation Management

  • Epinephrine is a Vesicant: extravasation can cause tissue necrosis
  • Technique to Manage Extravasation
    • Discontinue Epinephrine Infusion and Gently Aspirate the Extravasated Solution
    • Phentolamine (see Phentolamine, [[Phentolamine]]): dilute 5-10 mg in 10-15 mL of normal saline and administer into extravasation site as soon as possible after extravasation
    • Topical Nitroglycerin 2% Ointment (see Nitroglycerin, [[Nitroglycerin]]): apply a 1 inch strip to the affected site

Drug Interactions

  • Spironolactone (Aldactone) (see Spironolactone, [[Spironolactone]]): spironolactone may decrease the vasoconstrictor effect of α/β-adrenergic agonists
  • Inhalational Anesthetics: may increase the arrhythmogenic effect of epinephrine
  • MAO Inhibitors (see Monoamine Oxidase Inhibitors, [[Monoamine Oxidase Inhibitors]]): may enhance the hypertensive effect of vasopressors (epinephrine, etc) and other sympathomimetics
    • Linezolid (Zyvox) (see Linezolid, [[Linezolid]])
  • Lurasidone (Latuda) (see Lurasidone, [[Lurasidone]]): epinephrine may enhance the hypotensive effect of lurasidone
  • Serotonin Norepinephrine Reuptake Inhibitors (SNRI) (see Serotonin Norepinephrine Reuptake Inhibitors, [[Serotonin Norepinephrine Reuptake Inhibitors]]): SNRI’s may enhance the vasopressor effects of α/β-adrenergic agonists

Adverse Effects

Cardiovascular Adverse Effects

  • Arrhythmias
  • Exacerbation of Myocardial Ischemia (see Coronary Artery Disease, [[Coronary Artery Disease]])
    • Clinical
      • Acute Myocardial Infarction
      • Chest Pain/Angina (see Chest Pain, [[Chest Pain]])
  • Extravasation-Associated Tissue Necrosis
    • Epidemiology: associated with intravenous administration
  • Hypertension (see Hypertension, [[Hypertension]])
  • Palpitations (see Palpitations, [[Palpitations]])
  • QT Prolongation without Definite Association with Torsade (see Torsade, [[Torsade]])
  • Sinus Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])

Dermatologic Adverse Effects

Endocrinologic Adverse Effects

Gastrointestinal Aderse Effects

Neurologic Adverse Effects

Pulmonary Adverse Effects

  • Pulmonary Edema (see Pulmonary Edema, [[Pulmonary Edema]])
    • Pharmacology: due to peripheral vasoconstriction and cardiac stimulation

Renal Adverse Effects

  • Decreased Urine Output
    • Pharmcology: due to renal vasoconstriction

Rheumatologic/Orthopedic Adverse Effects

  • Acute Limb Ischemia/Digital Ischemia (see Acute Limb Ischemia, [[Acute Limb Ischemia]])
    • Pharmcology: due to vasoconstriction

References

  • Adrenaline administered via a nebulizer in adult patients with upper airway obstruction. Anaesthesia. 1995;50:35–6 [MEDLINE]
  • The effect of epinephrine by nebulization on measures of airway obstruction in patients with acute severe croup. Intensive Care Med. 2008;34:138–47
  • L-epinephrine and dexamethasone in postextubation airway obstruction: a prospective, randomized, double-blind placebo-controlled study. Int J Pediatr Otorhinolaryngol. 2009;73:1639–43 [MEDLINE]
  • Nebulized epinephrine for croup in children. Cochrane Database Syst Rev. 2013;10:CD006619 [MEDLINE]
  • Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review. Crit Care. 2015 Sep 23;19:295. doi: 10.1186/s13054-015-1018-2 [MEDLINE]