Epinephrine

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

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

General
1. Epinephrine has a short Half-Life: ~2 minutes
  1. As with other Catecholamines, Epinephrine is rapidly metabolized by COMT and MAO
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
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)

Anaphylaxis
Status Asthmaticus
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)
Post-Resuscitation Stabilization (Infusion)
1. Significant Bradycardia with hemodynamic instability
2. Poor systemic perfusion or Hypotension despite
  1. Intravascular volume replacement AND Stable rhythm

Symptomatic Bradycardia (with a pulse)
1. Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
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
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)

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
Start Dose: 20 ml/hour until Tachycardia
1. Indicates drug has entered circulation
Titrate Dose
1. Decrease to desired rate (0.1 - 1.0 ug/kg/min)
2. Adjust infusion rate every 5 min to desired effect

Rhythms
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
Repeat every 3-5 minutes
Consider increasing dose to 3 or 5 mg (0.1 mg/kg)

Indicated if repeat intramuscular Epinephrine dosing is required for Anaphylaxis
1. Ordered at the time of second IM Epinephrine dose
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
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)
References
1. Lin in Herbert (2014) EM Rap 14(1): 7

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

See Push Dose Pressor
See Intravenous Phenylephrine
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
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
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

See Guidelines for Emergency Cardiovascular Care
Epinephrine is recommended in most of the ACLS cardiac guidelines 2010 (recommendation 2B)
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