Epinephrine

Aka: Epinephrine, Adrenaline, Dirty Epinephrine Drip, Epinephrine Push Dose Pressor

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II. Definitions

  1. Epinephrine (Adrenaline)
    1. Natural Catecholamine, synthesized and released from the Adrenal Medulla as a stress response (along with Norepinephrine)
    2. Has both alpha and beta adrenergic activity

III. History

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

IV. Physiology

  1. General
    1. Epinephrine has a short Half-Life: ~2 minutes
      1. As with other Catecholamines, Epinephrine is rapidly metabolized by COMT and MAO
  2. Alpha Adrenergic Agonist Effects
    1. Most important medication in Cardiac Arrest and Anaphylaxis
    2. Vasoconstriction (a1)
      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
  3. Beta Adrenergic Agonist effects (Under 0.3 mcg/kg/min)
    1. Cardiac Effects
      1. Increases myocardial contractility (b1)
      2. Increases Heart Rate (b1)
    2. Lung Effects
      1. Relaxes Bronchial Smooth Muscle or bronchodilation (b2)
    3. Endocrine Effects
      1. Increases Serum Glucose via Gluconeogenesis and Glycogenolysis (b2)
      2. Increases Fatty Acids via fat cell lipolysis of Triglycerides (b1)
    4. Gastrointestinal and Genitourinary Effects
      1. Decreased intestinal tone and motility (alpha, b2)
      2. Urinary sphincter contraction (alpha)
      3. Uterine contraction outside of pregnancy (a1)
        1. Uterine relaxation in near-term and peripartum period (b2)

V. Indications

  1. Anaphylaxis
  2. Status Asthmaticus
  3. Initial Resuscitation Management (bolus)
    1. Cardiac Arrest (VT/VFib, PEA)
      1. Vasopressin may be used instead in some protocols
    2. Symptomatic Bradycardia unresponsive to other measures (oxygenation, ventilation)
    3. Hypotension refractory to volume replacement (see Vasopressor)
  4. Post-Resuscitation Stabilization (Infusion)
    1. Significant Bradycardia with hemodynamic instability
    2. Poor systemic perfusion or Hypotension despite
      1. Intravascular volume replacement AND Stable rhythm

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 Push Dose Pressor
  2. See Intravenous Phenylephrine
  3. Precautions
    1. Limit Push Dose Pressors to emergency use
    2. Mixing errors are common (Exercise caution)
    3. When adequate time is available, pharmacy prepared solutions are preferred
    4. Push Dose Pressors are a temporizing measure to stabilize Hypotension
      1. In some cases, Push Dose Pressor alone may be sufficient (e.g. Propofol induced Hypotension)
      2. Prepare for Vasopressor infusion (e.g. Norepinephrine, Epinephrine) if expected persistent Hypotension
  4. Preparation
    1. Start with 9 ml of Normal Saline in 10 ml syringe
    2. Draw 1 ml of Cardiac Epinephrine (100 mcg/ml or 0.1 mg/ml or 1 to 10:000 dilution) in vial
    3. Final Concentration: Epinephrine 10 mcg/ml
  5. 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

XV. References

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

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Cost: Medications

epinephrine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
EPINEPHRINE 0.15 MG AUTO-INJCT Generic $127.35 each
EPINEPHRINE 0.3 MG AUTO-INJECT Generic $137.05 each
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