II. Definition

  1. Natural Catecholamine with Alpha and beta activity

III. History

  1. Medical case report in 1923 on intracardiac Adrenaline
    1. Shown to reverse "Acute heart paralysis"

IV. Pathophysiology

  1. Alpha Adrenergic Agonist Effects
    1. Most important for Cardiac Arrest
    2. Vasoconstriction
      1. Increases Systemic Vascular Resistance
      2. Increases Systolic and Diastolic Blood Pressure
    3. Increases Vital Organ Perfusion
      1. Increases Myocardial perfusion
      2. Increases Cerebral perfusion
    4. Decreases Non-Vital Organ Perfusion
      1. Decreases splanchnic and intestinal perfusion
      2. Decreases renal perfusion
      3. Decreases skin perfusion
  2. Beta Adrenergic Agonist effects (Under 0.3 ug/kg/min)
    1. Increases myocardial contractility
    2. Increases Heart Rate
    3. Relaxes Bronchial smooth muscle (bronchodilation)
  3. Epinephrine has a short half-life: ~2 minutes

V. Indications

  1. Initial Resuscitation Management (bolus)
    1. Cardiac Arrest
      1. Vasopressin may be used instead in some protocols
    2. Symptomatic Bradycardia unresponsive to
      1. Oxygenation
      2. Ventilation
    3. Hypotension refractory to volume replacement
  2. Post-Resuscitation Stabilization (Infusion)
    1. Poor systemic perfusion or Hypotension despite
      1. Intravascular volume replacement AND
      2. Stable rhythm
    2. Significant Bradycardia

VI. Dosing: Newborn (refractory and persistant Bradycardia)

  1. Epinephrine (1:10,000) 0.1 to 0.3 ml/kg by IV or ET
  2. Do not use the 1:1000 concentration in newborns

VII. Dosing: Pediatric

  1. Symptomatic Bradycardia (with a pulse)
    1. Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
  2. Pulseless Cardiac Arrest
    1. Initial regular dose Epinephrine
      1. Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
    2. Subsequent High Dose Epinephrine (if no effect above)
      1. Dose: 0.1 mg/kg IV/IO (0.1 ml/kg of 1:1000 Epi)
      2. Maximum dose: 0.2 mg/kg
    3. Repeat dose every 3-5 minutes
  3. Endotracheal Administration
    1. Adults and children: 0.1 mg/kg (0.1 ml/kg of 1:1000)
    2. Newborn: 0.1 mg/kg (1 ml/kg of 1:10,000)

VIII. Dosing: Pediatric Infusion (Same as Isoproterenol preparation)

  1. Preparation
    1. Draw up "x" mg of Epinephrine
    2. Where "x" = 0.6 x WeightKg
    3. Add enough D5W or NS to Epinephrine for 100 ml total
    4. At this dilution
      1. Infusion rate of 1 ml/h provides 0.1 ug/kg/h
  2. Start Dose: 20 ml/hour until Tachycardia
    1. Indicates drug has entered circulation
  3. Titrate Dose
    1. Decrease to desired rate (0.1 - 1.0 ug/kg/min)
    2. Adjust infusion rate every 5 min to desired effect

IX. Dosing: Adult Pulseless Arrest

  1. Rhythms
    1. Asystole
    2. Pulseless Electrical Activity
    3. Ventricular Fibrillation
  2. Initial
    1. IV: 1 mg (10 ml of 1:10,000 Epi) IV push
    2. Endotracheal: 2.5 ml of 1:1000 Epi in 10 ml NS
  3. Repeat every 3-5 minutes
  4. Consider increasing dose to 3 or 5 mg (0.1 mg/kg)

X. Dosing: Anaphylaxis "Dirty" Epinephrine drip ("dirty epi drip")

  1. Indicated if repeat intramuscular Epinephrine dosing is required for Anaphylaxis
    1. Ordered at the time of second IM Epinephrine dose
  2. Preparation: Epinephrine 1 mcg/ml solution
    1. Draw up 1 mg of Epinephrine (1 ml of 1:1000 or 10 ml of 1:10000)
    2. Inject 1 mg Epinephrine into 1 Liter bag of Normal Saline (now 1 mcg/ml Epinephrine)
    3. Given 1 cc/20 drops AND 1 mcg/ml Epinephrine
      1. Goal rate: 6 mcg/min
      2. Equates to 2 drops per second
  3. Infusion: Epinephrine 1 mcg/ml solution
    1. Protocol 1: Hypotensive, unstable patient option 1
      1. Draw into syringe, 10 ml (10 mcg) from 1 mcg/ml Epinephrine solution prepared above
      2. Inject 5 ml (5 mcg) IV (may repeat second 5 ml/5 mcg dose)
    2. Protocol 2: Hypotensive, unstable patient option 2
      1. Open Epinephrine solution IV (flows at 20-50 mcg/min through 18 gauge IV)
      2. Provider stands by the bedside and closely controls infusion
        1. Titrate until patient hemodynamically stable
      3. Decrease the Epinephrine flow as patient becomes hemodynamically stable
      4. Decrease flow towards 1-4 mcg/min
        1. Wean as approach cummulative max IV Epinephrine dose
          1. Max cummulative dose: 100 mcg (3-5 min with open IV)
        2. Equivalent of the initial Anaphylaxis guideline
          1. Recommended bolus of 0.1 mg IV push over 5 minutes
    3. Protocol 3: Cautious titration
      1. Start infusion at 1 mcg/min and titrate to effect (typically 1-4 mcg/min)
  4. References
    1. Lin in Herbert (2014) EM Rap 14(1): 7

XI. Dosing: Adult Infusion for symptomatic Bradycardia

  1. Preparation
    1. Draw up 1 mg Epinephrine (1 ml of 1:1000)
    2. Add Epinephrine to 500 ml Normal Saline or D5W
  2. Start Dose: 1 ug/min
  3. Titrate Dose to desired effect (2-10 ug/min)

XII. Dosing: Adult Push Dose Pressor for Hypotension refractory to fluid bolus

  1. See Intravenous Phenylephrine
  2. Preparation
    1. Start with 9 ml of Normal Saline in 10 ml syringe
    2. Draw 1 ml of Cardiac Epinephrine (100 mcg/ml) in vial
    3. Final Concentration: Epinephrine 10 mcg/ml
  3. Dose
    1. Epinephrine (10 mcg/ml) 0.5 to 2 ml (5-20 mcg) every 2-5 minutes
    2. Expect onset of action within 1 minute and effect lasting 5-10 minutes

XIII. Precautions

  1. Carefully check concentration (1:1000 OR 1:10,000)
  2. Observe for side effects after Resuscitation
    1. Supraventricular Tachycardia
    2. Ventricular Tachycardia
    3. Severe Hypertension
  3. Extravasation into tissues
    1. may causes local ischemia or necrosis
  4. Can exacerbate Myocardial Ischemia
  5. Do not mix with alkaline solutions

XIV. Efficacy: Cardiac Arrest

  1. See Guidelines for Emergency Cardiovascular Care
  2. Epinephrine is recommended in most of the ACLS cardiac guidelines 2010 (recommendation 2B)
  3. More recent data since 2010 guidelines may lead to future modified recommendations (research topic only for now)
    1. Epinephrine appears to have no effect on neurologically intact survival despite significantly increasing rate of ROSC
      1. Jacobs (2011) Resuscitation 82(9): 1128-43 [PubMed]
      2. Nakahara (2013) BMJ 347: f6829 [PubMed]
    2. Early use of Epinephrine in Cardiac Arrest may be associated with better outcomes
      1. Nakahara (2012) Acad Emerg Med 19(7):782-92 [PubMed]
    3. Epinephrine has theoretical risks in Cardiac Arrest
      1. Tachydysrhthythmias
      2. Increased myocardial oxygen demand
      3. Thrombogenesis
    4. References
      1. Swaminathan and Hayes in Herbert (2014) EM:Rap 14(6): 7-8

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Cost: Medications

epinephrine (on 4/20/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
EPINEPHRINE 0.1 MG/ML SYRINGE Generic $0.43 per ml
EPINEPHRINE 0.15 MG AUTO-INJCT Generic $193.79 each
EPINEPHRINE 0.3 MG AUTO-INJECT Generic $199.24 each
EPINEPHRINE 1 MG/ML AMPUL Generic $1.97 per ml

Ontology: Epinephrine (C0014563)

Definition (MSH) The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
Definition (CHV) a kind of hormone
Definition (CHV) a kind of hormone
Definition (NCI) The synthetic form of the naturally occurring sympathomimetic amine with vasoconstricting, intraocular pressure-reducing, and bronchodilating activities. By stimulating vascular alpha-adrenergic receptors, epinephrine causes vasoconstriction, thereby increasing vascular resistance and blood pressure. When administered in the conjunctiva, this agent binds to alpha-adrenergic receptors in the iris sphincter muscle, resulting in vasoconstriction, a decrease in the production of aqueous humor, and a lowering of intraocular pressure. Through its beta1 receptor-stimulating actions, epinephrine increases the force and rate of myocardial contraction and relaxes bronchial smooth muscle, resulting in bronchodilation.
Definition (NCI_NCI-GLOSS) A hormone and neurotransmitter.
Definition (CSP) active sympathomimetic hormone from the adrenal medulla in most species; it stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels; used in treatment of asthma and cardiac failure and to delay absorption of local anesthetics.
Definition (PDQ) The synthetic form of the naturally occurring sympathomimetic amine with bronchodilating, intraocular pressure reducing, and vasoconstricting activity. By stimulating alpha adrenergic receptors, this agent causes vasoconstriction, thereby increasing vascular resistance and blood pressure. When administered in the conjunctiva, epinephrine binds to alpha-adrenergic receptors in the iris sphincter muscle, thereby causing vasoconstriction and a decrease in the production of aqueous humor. Through its beta1-receptor stimulating actions, this agent increases the force and rate of myocardial contraction and relaxes bronchial smooth muscle, thereby causing bronchodilatation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41857&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41857&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C473" NCI Thesaurus)
Concepts Organic Chemical (T109) , Hormone (T125) , Neuroreactive Substance or Biogenic Amine (T124) , Pharmacologic Substance (T121)
MSH D004837
SnomedCT 65502005, 320288006, 319480007, 354037007, 391721000, 259342005, 372575003, 78890004, 387362001
LNC LP15027-3, MTHU002341
English Adrenaline, Epinephrine, 4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol, 1,2-Benzenediol, 4-(1-hydroxy-2-(methylamino)ethyl)-, (R)-, Adrenaline [card], Adrenaline [resp], therapeutic epinephrine, Adrenaline [cardiovascular use], Adrenaline [resp] (product), Adrenaline [cardiovascular use] (product), epinephrine (medication), adrenalin, sympathomimetics epinephrine, Adrenalin, epinephrine, Epinephrine [Chemical/Ingredient], EPINEPHRINE, EPINEPHrine, Adrenaline product (product), Epinephrine [cardiovascular use] (product), Adrenaline - chemical (substance), Adrenaline (product), Epinephrine [resp], Adrenaline - chemical, Epinephrine [cardiovascular use], Epinephrine [resp] (product), adrenaline, Adrenal, Adrenaline preparation, Adrenaline product, Epinephrine preparation, Epinephrine (substance), Epinephrine preparation (product), Epinephrine product, Epinephrine (substance) [Ambiguous], Epinephrine preparation (substance), Adrenaline (substance), Adrenaline [cardiovascular use] (substance), Adrenaline [resp] (substance), Epi, Therapeutic Epinephrine
Swedish Adrenalin
Spanish preparado de adrenalina, Adrenaline (substance), preparado con adrenalina (producto), preparado con epinefrina, epinefrina (producto), adrenalina, preparado con adrenalina, adrenalina (producto), adrenalina (uso cardiovascular), epinefrina (uso cardiovascular), adrenalina [resp] (producto), adrenalina (sustancia), Adrenaline, adrenalina [resp], adrenalina (uso cardiovascular) (producto), adrenalina (concepto no activo), preparado de adrenalina (concepto no activo), preparado de adrenalina (sustancia), preparado de adrenalina (producto), preparado de epinefrina, epinefrina, epinefrina (sustancia), Epinefrina, Adrenalina
Czech adrenalin, epinefrin
Finnish Adrenaliini
French Adrénaline, Épinéphrine
Italian 4-(1-Idrossi-2-(metilamino)etil)-1,2-benzenediolo, Adrenalina, Epinefrina
Russian ADRENALIN, EPINEFRIN, АДРЕНАЛИН, ЭПИНЕФРИН
Japanese サンエピ, エピスタ, アドレナリン, バポネフリン, エピネフリン, エピクィック, ボスミン
Croatian EPINEFRIN
Polish Adrenalina, Epinefryna
Norwegian Adrenalin, Epinefrin
German Adrenalin, Epinephrin
Portuguese Adrenalina, Epinefrina