II. Definitions
- Epinephrine (Adrenaline)
- Natural Catecholamine, synthesized and released from the Adrenal Medulla as a stress response (along with Norepinephrine)
- Has both alpha and beta adrenergic activity
III. History
- Medical case report in 1923 on intracardiac Adrenaline
- Shown to reverse "Acute heart paralysis"
IV. Physiology
-
General
- Epinephrine has a short Half-Life: ~2 minutes
- As with other Catecholamines, Epinephrine is rapidly metabolized by COMT and MAO
- Epinephrine has a short Half-Life: ~2 minutes
-
Alpha Adrenergic Agonist Effects
- Most important medication in Cardiac Arrest and Anaphylaxis
- Vasoconstriction (a1)
- Increases Systemic Vascular Resistance
- Increases Systolic and Diastolic Blood Pressure
- Increases Vital Organ Perfusion
- Increases Myocardial perfusion
- Increases Cerebral perfusion
- Decreases Non-Vital Organ Perfusion
- Decreases splanchnic and intestinal perfusion
- Decreases renal perfusion
- Decreases skin perfusion
-
Beta Adrenergic Agonist effects (Under 0.3 mcg/kg/min)
- Cardiac Effects
- Increases myocardial contractility (b1)
- Increases Heart Rate (b1)
- Lung Effects
- Relaxes Bronchial Smooth Muscle or bronchodilation (b2)
- Endocrine Effects
- Increases Serum Glucose via Gluconeogenesis and Glycogenolysis (b2)
- Increases Fatty Acids via fat cell lipolysis of Triglycerides (b1)
- Gastrointestinal and Genitourinary Effects
- Decreased intestinal tone and motility (alpha, b2)
- Urinary sphincter contraction (alpha)
- Uterine contraction outside of pregnancy (a1)
- Uterine relaxation in near-term and peripartum period (b2)
- Cardiac Effects
V. Indications
- Anaphylaxis
- Status Asthmaticus
- Initial Resuscitation Management (bolus)
- Cardiac Arrest (VT/VFib, PEA)
- Vasopressin may be used instead in some protocols
- Symptomatic Bradycardia unresponsive to other measures (oxygenation, ventilation)
- Hypotension refractory to volume replacement (see Vasopressor)
- Cardiac Arrest (VT/VFib, PEA)
- Post-Resuscitation Stabilization (Infusion)
- Significant Bradycardia with hemodynamic instability
- Poor systemic perfusion or Hypotension despite
- Intravascular volume replacement AND Stable rhythm
VI. Dosing: Newborn (refractory and persistant Bradycardia)
- Epinephrine (1:10,000) 0.1 to 0.3 ml/kg by IV or ET
- Do not use the 1:1000 concentration in newborns
VII. Dosing: Pediatric
-
Symptomatic Bradycardia (with a pulse)
- Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
-
Pulseless Cardiac Arrest
- Initial regular dose Epinephrine
- Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
- Subsequent High Dose Epinephrine (if no effect above)
- Dose: 0.1 mg/kg IV/IO (0.1 ml/kg of 1:1000 Epi)
- Maximum dose: 0.2 mg/kg
- Repeat dose every 3-5 minutes
- Initial regular dose Epinephrine
- Endotracheal Administration
- Adults and children: 0.1 mg/kg (0.1 ml/kg of 1:1000)
- Newborn: 0.1 mg/kg (1 ml/kg of 1:10,000)
VIII. Dosing: Pediatric Infusion (Same as Isoproterenol preparation)
- Preparation
- Draw up "x" mg of Epinephrine
- Where "x" = 0.6 x WeightKg
- Add enough D5W or NS to Epinephrine for 100 ml total
- At this dilution
- Infusion rate of 1 ml/h provides 0.1 ug/kg/h
- Start Dose: 20 ml/hour until Tachycardia
- Indicates drug has entered circulation
- Titrate Dose
- Decrease to desired rate (0.1 - 1.0 ug/kg/min)
- Adjust infusion rate every 5 min to desired effect
IX. Dosing: Adult Pulseless Arrest
- Rhythms
- Initial
- IV: 1 mg (10 ml of 1:10,000 Epi) IV push
- 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)
X. Dosing: Anaphylaxis "Dirty" Epinephrine drip ("dirty epi drip")
- Indicated if repeat intramuscular Epinephrine dosing is required for Anaphylaxis
- Ordered at the time of second IM Epinephrine dose
- Preparation: Epinephrine 1 mcg/ml solution
- Draw up 1 mg of Epinephrine (1 ml of 1:1000 or 10 ml of 1:10000)
- Inject 1 mg Epinephrine into 1 Liter bag of Normal Saline (now 1 mcg/ml Epinephrine)
- Given 1 cc/20 drops AND 1 mcg/ml Epinephrine
- Goal rate: 6 mcg/min
- Equates to 2 drops per second
- Infusion: Epinephrine 1 mcg/ml solution
- Protocol 1: Hypotensive, Unstable Patient option 1
- Draw into syringe, 10 ml (10 mcg) from 1 mcg/ml Epinephrine solution prepared above
- Inject 5 ml (5 mcg) IV (may repeat second 5 ml/5 mcg dose)
- Protocol 2: Hypotensive, Unstable Patient option 2
- Open Epinephrine solution IV (flows at 20-50 mcg/min through 18 gauge IV)
- Provider stands by the bedside and closely controls infusion
- Titrate until patient hemodynamically stable
- Decrease the Epinephrine flow as patient becomes hemodynamically stable
- Decrease flow towards 1-4 mcg/min
- Wean as approach cummulative max IV Epinephrine dose
- Max cummulative dose: 100 mcg (3-5 min with open IV)
- Equivalent of the initial Anaphylaxis guideline
- Recommended bolus of 0.1 mg IV push over 5 minutes
- Wean as approach cummulative max IV Epinephrine dose
- Protocol 3: Cautious titration
- Start infusion at 1 mcg/min and titrate to effect (typically 1-4 mcg/min)
- Protocol 1: Hypotensive, Unstable Patient option 1
- References
- Lin in Herbert (2014) EM Rap 14(1): 7
XI. Dosing: Adult Infusion for Symptomatic Bradycardia
- Preparation
- Draw up 1 mg Epinephrine (1 ml of 1:1000)
- Add Epinephrine to 500 ml Normal Saline or D5W
- Start Dose: 1 ug/min
- Titrate Dose to desired effect (2-10 ug/min)
XII. Dosing: Adult Push Dose Pressor for Hypotension refractory to fluid bolus
- See Push Dose Pressor
- See Intravenous Phenylephrine
- Precautions
- Limit Push Dose Pressors to emergency use
- Mixing errors are common (Exercise caution)
- When adequate time is available, pharmacy prepared solutions are preferred
- Push Dose Pressors are a temporizing measure to stabilize Hypotension
- In some cases, Push Dose Pressor alone may be sufficient (e.g. Propofol induced Hypotension)
- Prepare for Vasopressor infusion (e.g. Norepinephrine, Epinephrine) if expected persistent Hypotension
- Preparation
- Start with 9 ml of Normal Saline in 10 ml syringe
- Draw 1 ml of Cardiac Epinephrine (100 mcg/ml or 0.1 mg/ml or 1 to 10:000 dilution) in vial
- Final Concentration: Epinephrine 10 mcg/ml
- Dose
- Epinephrine (10 mcg/ml) 0.5 to 2 ml (5-20 mcg) every 2-5 minutes
- Expect onset of action within 1 minute and effect lasting 5-10 minutes
XIII. Precautions
- Carefully check concentration (1:1000 OR 1:10,000)
- Observe for side effects after Resuscitation
- Extravasation into tissues
- may causes local ischemia or necrosis
- Can exacerbate Myocardial Ischemia
- Do not mix with alkaline solutions
XIV. Efficacy: Cardiac Arrest
- 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)
- Epinephrine appears to have no effect on neurologically intact survival despite significantly increasing rate of ROSC
- Early use of Epinephrine in Cardiac Arrest may be associated with better outcomes
- Epinephrine has theoretical risks in Cardiac Arrest
- Tachydysrhthythmias
- Increased myocardial oxygen demand
- Thrombogenesis
- References
- Swaminathan and Hayes in Herbert (2014) EM:Rap 14(6): 7-8
XV. References
- Olson (2020) Clinical Pharmacology, Medmasters, Miami, p. 13-33
- Goldstein (2010) Clin Auton Res 20(6):331-52 +PMID: 20623313 [PubMed]
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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 |