Pharm
Epinephrine
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Epinephrine
, Adrenaline, Dirty Epinephrine Drip, Epinephrine Push Dose Pressor
See Also
Norepinephrine
Sympathetic Nervous System
Sympathomimetic
Alpha Adrenergic Receptor
Beta Adrenergic Receptor
Sympathomimetic Toxicity
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
History
Medical case report in 1923 on intracardiac Adrenaline
Shown to reverse "Acute heart paralysis"
Physiology
Gene
ral
Epinephrine has a short
Half-Life
: ~2 minutes
As with other
Catecholamine
s, Epinephrine is rapidly metabolized by COMT and MAO
Alpha Adrenergic Agonist
Effects
Most important medication in
Cardiac Arrest
and
Anaphylaxis
Vasocon
striction (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
Bronchi
al
Smooth Muscle
or bronchodilation (b2)
Endocrine Effects
Increases
Serum Glucose
via
Gluconeogenesis
and Glycogenolysis (b2)
Increases
Fatty Acid
s via fat cell lipolysis of
Triglyceride
s (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)
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
)
Post-
Resuscitation
Stabilization (Infusion)
Significant
Bradycardia
with hemodynamic instability
Poor systemic perfusion or
Hypotension
despite
Intravascular volume replacement AND Stable rhythm
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
Dosing
Pediatric
Symptomatic Bradycardia
(with a pulse)
Dose: 0.01 mg/kg IV/IO (0.1 ml/kg of 1:10,000 Epi)
Pulse
less
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
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)
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
Dosing
Adult
Pulse
less Arrest
Rhythms
Asystole
Pulseless Electrical Activity
Ventricular Fibrillation
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)
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
Protocol 3: Cautious titration
Start infusion at 1 mcg/min and titrate to effect (typically 1-4 mcg/min)
References
Lin in Herbert (2014) EM Rap 14(1): 7
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)
Dosing
Adult
Push Dose Pressor
for
Hypotension
refractory to fluid bolus
See
Push Dose Pressor
See
Intravenous Phenylephrine
Precautions
Limit
Push Dose Pressor
s to emergency use
Mixing errors are common (
Exercise
caution)
When adequate time is available, pharmacy prepared solutions are preferred
Push Dose Pressor
s 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
Precautions
Carefully check concentration (1:1000 OR 1:10,000)
Observe for side effects after
Resuscitation
Supraventricular Tachycardia
Ventricular Tachycardia
Severe Hypertension
Extravasation into tissues
may causes local ischemia or necrosis
Can exacerbate
Myocardial Ischemia
Do not mix with alkaline solutions
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
Jacobs (2011) Resuscitation 82(9): 1128-43 [PubMed]
Nakahara (2013) BMJ 347: f6829 [PubMed]
Early use of Epinephrine in
Cardiac Arrest
may be associated with better outcomes
Nakahara (2012) Acad Emerg Med 19(7):782-92 [PubMed]
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
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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