Epinephrine

Class: alpha- and beta-Adrenergic Agonists
VA Class: AU100
CAS Number: 51-43-4
Brands: Adrenalin Chloride, EpiPen Auto-Injector, EpiPen Jr., Primatene

Introduction

Epinephrine is an endogenous catecholamine that is the active principle of the adrenal medulla; epinephrine acts directly on both α- and β-adrenergic receptors.

Uses for Epinephrine

Bronchospasm

Has been used as as a quick-relief bronchodilator for symptomatic treatment of acute symptoms and exacerbations of bronchial asthma and reversible bronchospasm associated with chronic bronchitis, emphysema, and other obstructive pulmonary diseases.^{a 160 162 166 168} However, generally should be used only when selective β₂-agonists are not readily available, since excessive cardiac stimulation (e.g., increased heart rate, myocardial irritability, increased oxygen demand) can occur with nonselective agents, particularly at high doses.^{160 162 174 d}

Orally inhaled selective β₂-agonists currently are recommended for prehospital management of asthma exacerbations (e.g., in emergency medicine facilities and/or ambulances) and for acute asthma management in emergency rooms and hospitals.^{160 161 162} Reserve sub-Q epinephrine for severe exacerbations when selective agents are not readily available or are ineffective.^{160 161 162 174 d} No proven advantage of systemically administered (e.g., sub-Q) epinephrine therapy over orally inhaled therapy for the acute management of asthma exacerbations.^{160 162} Parenteral epinephrine may be particularly useful in treating anaphylaxis and angioedema coexisting with asthma.¹⁷⁴

Nebulized bronchodilator therapy generally should be reserved for patients who are unable to coordinate inhalation via an MDI because of their age, agitation, or exacerbation severity.¹⁶⁰

Regular, daily use of a short-acting, inhaled β-agonist generally is no longer recommended for maintenance therapy of asthma.¹⁶⁰ Current asthma guidelines emphasize long-term control with anti-inflammatory agents (e.g., corticosteroids), and concomitant anti-inflammatory therapy with an inhaled corticosteroid is recommended whenever inhaled β-agonist bronchodilators are used for maintenance.^{130 131 132 138 140 141 147 148}

Sensitivity Reactions

Drug of choice in the emergency treatment of severe acute anaphylactic reactions, including anaphylactic shock, which can be profound and life-threatening.^{a 161 163 164 d}

May relieve anaphylactic symptoms (e.g., urticaria, pruritus, angioedema, wheezing, dyspnea, hypotension, swelling of the lips, eyelids, and tongue) caused by reactions to drugs, contrast media, sera, insect stings or bites, foods (e.g., milk, eggs, fish, shellfish, peanuts, tree nuts), latex, or other allergens as well as idiopathic or exercise-induced anaphylaxis.^{a 161 163 d}

Give to all patients with signs of shock, airway swelling, or definite breathing difficulty.^{161 d} Drug of choice for the treatment of both vasodilation/hypotension and cardiac arrest associated with anaphylaxis.^{161 d}

Parenteral administration (IM route favored)^d is preferred for the treatment of anaphylaxis.^{a d} Administer IV if anaphylaxis appears to be severe with immediate life-threatening manifestations.^{161 d} Absorption and subsequent achievement of peak plasma concentrations after sub-Q injection is slower and may be substantially delayed in patients with shock.^{161 d}

High IV doses (i.e., rapid progression to high dose) should be used without hesitation in any patient in full cardiac arrest.^{161 d}

If necessary, institute other measures for management of cardiac arrhythmias, laryngeal edema, or bronchospasm.^a Once adequate ventilation is ensured, maintenance of BP in anaphylactic shock should be achieved with other pressor agents (e.g., norepinephrine, metaraminol).^a

Close monitoring critical; fatal overdose of epinephrine reported.^d

Risk of paradoxical response to epinephrine in patients receiving β-adrenergic blocking agents; consider glucagon and/or ipratropium for treatment of anaphylaxis in these patients.^d Increased incidence and severity of anaphylaxis in patients receiving β-adrenergic blocking agents.^d

CPR and Cardiac Arrhythmias

Used for its α-adrenergic stimulatory effects to increase blood flow in ACLS during CPR.^{a 161 d} The principal beneficial effects in patients with cardiac arrest result from increases in aortic diastolic blood pressure and in myocardial and cerebral blood flow during resuscitation.^{a 161 d} The value and safety of the β-adrenergic effects are controversial because they may increase myocardial work and reduce subendocardial perfusion.^{161 d}

A drug of choice and a high priority for ACLS in cardiac arrest to facilitate return of spontaneous circulation (ROSC); generally used after failure of artificial ventilation, external or internal cardiac compression, and initial defibrillation to restore effective circulation.^{a 161 d}

Cardiac arrest: May be administered IV, intraosseously, or intracardially or by direct instillation into the tracheobronchial tree via an endotracheal tube to restore cardiac rhythm as an adjunct in the management of cardiac arrest.^{a 161 169 170 d}

Asystole: Restores cardiac electrical activity in asystole and, in some cases, restores myocardial contractility in electromechanical dissociation.^{a 161}

Impending pulseless electrical activity: May produce beneficial vasopressor effects in patients who are not in cardiac arrest but who have other indications for vasopressor therapy¹⁶¹ (e.g., in those with severe bradycardia and hypotension who are close to pulseless electrical activity or even asystole).^a

Bradycardia: Treatment of symptomatic bradycardia unresponsive to atropine, as a temporizing measure while awaiting availability of a pacemaker (e.g., out-of-hospital setting) or if pacing ineffective.^d

Drug-induced cardiovascular emergencies or altered vital signs: May consider use in bradycardia or shock associated with β-adrenergic or calcium-channel blocking agent or tricyclic antidepressant toxicity.^d

Anesthesia accidents: May be useful in treating cardiac arrest following anesthesia accidents, but should be used with extreme caution, if at all, in patients receiving cyclopropane or halogenated hydrocarbon general anesthetics.^a (See General Anesthetics under Interactions.)

Heart block: Has been used in the treatment of syncope and/or bradycardia resulting from AV nodal block, but has largely been replaced by isoproterenol.^a Electrical cardiac pacemakers have largely replaced drug therapy in third-degree AV nodal block (complete heart block).^a

Radiographic Uses

Has been given intra-arterially† as an adjunct to radiographic contrast media in arteriography†.^a

GI and Renal Hemorrhage

Has been administered intra-arterially† via the celiac artery, inferior mesenteric artery, or superior mesenteric artery to control hemorrhage in patients with severe GI bleeding†.^a

Has been administered intra-arterially† via the renal artery to control hemorrhage in patients with renal arterial bleeding†.^a

Radiation Nephritis

Has been injected into a renal artery prior to and during irradiation of the abdominal area to protect the kidney from radiation nephritis†.^a

Adjunct to Local Anesthesia

May be added to solutions of some local anesthetics to decrease the rate of their vascular absorption (to localize and prolong the duration of anesthesia and decrease the risk of systemic toxicity).^a

Superficial Bleeding

May be applied topically to control superficial bleeding from arterioles or capillaries in the skin, mucous membranes, or other tissues.^a Bleeding from larger vessels is not controllable by topical application.^a

Cardiogenic, Hemorrhagic, and Traumatic Shock

Should not be used in cardiogenic shock (because it increases myocardial oxygen demand) or in hemorrhagic or traumatic shock.^a

Premature Labor

Has been used to relax uterine musculature and inhibit uterine contractions in premature labor† (tocolysis); however, the cardiovascular and other adverse effects limit its usefulness.^a (See Pregnancy under Cautions.) Other β-agonists (e.g., terbutaline) preferred.^{165 173}

Hypoglycemia

Has been used parenterally to correct hypoglycemia† in insulin shock; however, dextrose and/or glucagon is more effective.^a

Epinephrine Dosage and Administration

Administration

Administer by sub-Q, IM, or IV injection or by IV infusion.^{a 160 161 162 163 164 169 d} Also may be administered intra-arterially† (e.g., for radiography, for local control of bleeding).^a

In extreme cardiac emergencies, may be administered intracardially, via an endotracheal tube, or by intraosseous infusion†.^{a 161 169 170} Although endotracheal administration of epinephrine is possible, IV or intraosseous† administration is preferred because of more predictable drug delivery and pharmacologic effect.^d

Rapid IV injection (bolus dose) or endotracheal administration of epinephrine may cause failure of exhaled carbon dioxide detectors (used to confirm endotracheal tube placement in the trachea during cardiac arrest) despite adequate placement (i.e., false-negative reading).^d Use a second method to confirm tube placement.^d

For bronchodilation, administer by oral inhalation via a metered-dose inhaler (MDI), nebulization, or intermittent positive-pressure breathing (IPPB) apparatus or inject sub-Q or IM.^{a 160 162 166 168}

Apply topically to the skin and mucous membranes for local hemostasis.^a

Sub-Q Injection

Injections containing 1 mg/mL preferably are administered sub-Q.^{a 160 162 169} However, absorption and subsequent achievement of peak plasma concentrations is slower and may be substantially delayed if shock is present.^{a 161 d}

IM Injection

Injections containing 1 mg/mL also may be injected IM, but IM injection into the buttocks should be avoided.^{a 160 161 162 169 172 d}

For self-medication, instruct patients and their caregivers about proper administration techniques using the auto-injector provided by the manufacturer.^{163 164 d} First aid providers should be familiar with the auto-injector in order to assist patients having an anaphylactic reaction with self-medication, and they should be able to administer the auto-injector, if a patient is unable to self-administer, provided that state law permits it and valid prescription exists.^d

Technique for Using Auto-injector

Inject the age-appropriate dose IM only into the anterolateral aspect of the thigh.^{163 164}

The patient should grasp the prefilled auto-injector with the black tip pointed downward; the grey activation cap should be removed.¹⁶⁴ Point the black tip toward the outer thigh, swing and jab it firmly into the outer thigh so that the auto-injector is perpendicular (90° angle) to the thigh, and hold firmly in the thigh for several seconds until the dose is delivered.¹⁶⁴ Administer through clothing if necessary.¹⁶³ Massage injection area for several seconds.¹⁶⁴ If the needle is not exposed at the black tip, repeat administration.¹⁶⁴

Never put thumb, fingers, or hand over the black tip.¹⁶⁴

Do not remove the grey activation cap until ready to use.¹⁶⁴

The auto-injector is overfilled and most of the solution (90%) will remain after injection of the age-approriate dose and cannot be reused.¹⁶⁴

After use, bend the needle back against a hard surface.¹⁶⁴ Then, deliver the used auto-injector to a health-care provider for proper disposal.¹⁶⁴

IV Administration

Emergency situations: Inject very slowly IV as a dilute solution or infuse slowly IV.^a When injected peripherally, 1–2 minutes generally are required to reach central circulation.^{161 d}

Severe asthma or anaphylaxis: IV therapy may be necessary (e.g., for severe anaphylactic shock with immediate life-threatening manifestations) when drug absorption from sub-Q or IM injection is likely to be impaired.^{a d}

CPR: When a vein has not been cannulated prior to the arrest, a peripheral vein (antecubital or external jugular in adults and the largest most accessible vein that does not interrupt resuscitation in pediatric patients) is preferred since central venous access requires interruption of chest compressions, is technically more difficult, and is associated with an increased risk of complications.¹⁶¹ Venous access can be challenging in infants and children during an emergency, whereas intraosseous access can be easily achieved.^d Limit the time attempting venous access; if reliable access cannot be achieved quickly, establish intraosseous access.^d

If a central venous catheter is already in place at the time of arrest, it can be used because of more rapid onset (in adults), more secure access to circulation, and avoidance of tissue infiltration.^{161 d} Tissue infiltration may lead to local ischemia, tissue injury, and ulceration.^d Avoid central venous line placement in patients who are candidates for pharmacologic reperfusion (e.g., with thrombolytic therapy).^{161 d}

Dilution

Prepare infusion solutions containing 2 or 4 mcg/mL by adding 1 mg to 500 or 250 mL of a compatible IV solution, respectively.^{a 101 d}

Prepare solutions containing 0.05 mg/mL by adding 0.5 mg (0.5 mL of a 1:1000 injection) to 10 mL of 0.9% sodium chloride injetion.¹⁶⁹

Prepare a 1:10,000 solution (0.1 mg/mL) by diluting 1 mL of a commercially available 1:1000 injection (1 mg/mL) with 10 mL of water for injection or 0.9% sodium chloride injection.^a Alternatively, a commercially available 1:10,000 (0.1 mg/mL) injection can be used.¹⁷⁰

Prepare a 1:100,000 solution (0.01 mg/mL) by diluting 0.1 mL of a commercially available 1:1000 injection (1 mg/mL) with 10 mL of 0.9% sodium chloride injection.^a

Rate of Administration

Severe asthma or anaphylaxis: Inject IV slowly (e.g., over 5–10 minutes) or administer by rapid IV injection (i.e., bolus).^{a 101}

Alternatively in adults, infuse IV at an initial rate of 1 mcg/minute, increasing to 4 mcg/minute as needed.^a

In children after an initial 1-mcg/kg IV bolus, infuse IV at an initial rate of 0.1 mcg/kg per minute, increasing gradually up to 1.5 mcg/kg per minute as needed.¹⁰¹

CPR: Inject doses by IV push in adults, repeating at 3- to 5-minute intervals as needed;^{161 170 d} follow each dose injected peripherally with a 20-mL flush of IV fluid to ensure distribution into the central compartment;^{161 d} if injected IV in an extremity, elevate the extremity for 10–20 seconds.^d

In children, infuse IV at an initial rate of 0.1 mcg/kg per minute, increasing gradually to a maximum of 1 mcg/kg per minute as needed for CPR.^{a d}

Bradycardia or hypotension (i.e., nonarrest rate): In adults, infuse IV at an initial rate of 1 mcg/minute, titrating to hemodynamic response at rates ranging from 2–10 mcg/minute.^{161 d} Assess intravascular volume and support as needed.^d

In children, infuse IV at a rate of 0.1–0.2 mcg/kg per minute for refractory bradycardia.¹⁶¹

Intra-arterial Administration

Injections have been administered intra-arterially† for local effects (e.g., to control local bleeding, prevent radiation nephritis, as an adjunct to arteriography).^a

Rate of Administration

GI hemorrhage: 8–20 mcg/minute infused into the celiac or inferior or superior mesenteric artery†.^a

Renal hemorrhage: 10 mcg/minute infused into the renal artery†.^a

Radiation nephritis: 3–7.6 mcg/minute infused into the renal artery†.^a

Adjunct to arteriography: 8–12 mcg/minute infused into the celiac or superior mesenteric artery†.^a

Intracardiac Injection

Limit intracardiac injection to personnel well trained in the technique and generally use only during open cardiac massage or when other routes of administration are persistently inaccessible.^{a 161 170}

Inject into the left ventricular chamber.¹⁷⁰

Follow intracardiac administration by external cardiac massage to ensure entry of the drug into the coronary circulation.^a

Suspensions must not be administered intracardially.^a

Administration Risks

Hazards include coronary artery laceration, cardiac tamponade, pneumothorax, and the need to interrupt external chest compressions and ventilation during the period of administration.^{a 161}

Endotracheal Administration

Limit endotracheal administration to personnel well trained in the technique.^{a 161}

In intubated patients, doses can be instilled directly into the bronchial tree via the endotracheal tube.¹⁷⁰

Pass a catheter beyond the tip of the tracheal tube, stop chest compressions, inject the drug solution directly into the tracheal tube, follow immediately with several quick insufflations to create a rapidly absorbed aerosol, and then resume compressions.^{161 d}

For pediatric patients, flush with a minimum of 5 mL of 0.9% sodium chloride injection after each dose.^d

For pediatric patients, administration via a tracheal tube is preferred to a catheter or feeding tube because these latter 2 methods often are cumbersome and depend on finding the correct-size catheter to place through the tracheal tube.¹⁶¹

Dilution

Adults: Dilute dose in 5–10 mL of 0.9% sodium chloride or sterile water.^{a d} Systemic absorption may be increased by diluting in sterile water instead of 0.9% sodium chloride;^{a d} however, sterile water may have a more negative effect on arterial oxygen pressure (PaO₂) than sodium chloride.^a Alternatively, a commercially available 1:10,000 (0.1 mg/mL) injection may be administered undiluted via the endotracheal tube.¹⁷⁰

Intraosseous Administration

When IV administration is not possible, epinephrine may be given by intraosseous administration for emergency uses such as CPR.^{161 d}

Limit intraosseous administration to personnel well trained in the technique.^{a 161}

Place a cannula in a noncollapsible marrow venous plexus; such access often can be achieved in 30–60 seconds.¹⁶¹

Use a rigid needle, preferably a specially designed intraosseous or Jamshidi-type bone marrow needle; a styleted needle is preferred to prevent obstruction of the needle with cortical bone.¹⁶¹

Insert the intraosseous needle into the anterior tibial bone marrow; alternatively, the distal femur, medial malleolus, or anterior superior iliac spine can be used.¹⁶¹

In older children and adults, intraosseous cannulas also have been inserted successfully into the distal radius or ulna as well as the proximal tibia.¹⁶¹

Successful intraosseous placement outside the hospital (e.g., by emergency medical services) generally is more difficult in older than in younger children.¹⁶¹

Onset of action and systemic concentrations are comparable to those achieved with central venous administration.^{161 d}

Administration Risks

Complications are uncommon (less than 1% of patients), and include tibial fracture, lower-extremity compartment syndrome, extravasation, and osteomyelitis; careful technique can minimize the risk.¹⁶¹ Local effects on bone marrow and bone growth appear to be minimal.¹⁶¹ Risk of microscopic pulmonary fat and bone marrow emboli does not appear to be increased.¹⁶¹

Oral Inhalation

Epinephrine base or hydrochloride may be administered via oral inhalation using a nebulizer, aerosol (metered-dose inhaler [MDI]), or intermittent positive-pressure breathing (IPPB) apparatus.^{a 166 168}

For nebulization, use a glass or plastic nebulizer capable of delivering a very fine mist and that works effectively with a very small volume of solution.¹⁶⁸ Place the dose in the nebulizer reservoir and then place the nozzle just inside the partially opened mouth.¹⁶⁸ Squeeze the bulb once or twice, inhaling deeply to draw the vaporized solution into the lungs.¹⁶⁸ Rinse mouth with water immediately to prevent oropharyngeal dryness.¹⁶⁸

Solutions intended for oral inhalation are more concentrated than those intended for injection and must not be administered parenterally.^{a 168}

Do not administer oral inhalation solutions intranasally.¹⁶⁸

Topical Administration

Apply solutions topically as a spray or on cotton or gauze to the skin, mucous membranes, or other tissues.^a

Dosage

Available as epinephrine and epinephrine hydrochloride; dosage expressed in terms of epinephrine.^{a 163 166 168}

Pediatric Patients

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

Children ≥4 years of age: 220 mcg (1 inhalation) of epinephrine via an MDI, repeated once if necessary after at least 1 minute; do not administer subsequent doses for at least 3 hours.^{a 166}

Children ≥4 years of age: After placing approximately 10 drops of 1% (1:100) epinephrine in the nebulizer reservoir, administer 1–3 deep inhalations via the hand-bulb.^{a 168} Do not repeat more often than every 3 hours; use the least number of inhalations producing relief.^{a 168}

Sub-Q

For severe asthma, inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection)^{a 160 162} or 0.3 mg/m² (0.3 mL/m² of a 1:1000 injection) sub-Q.^{a 169}

Single pediatric doses should not exceed 0.3–0.5 mg every 20 minutes as needed for up to 3 consecutive doses.^{160 162 a 160 162 169}

IV

Neonates: Inject 0.01 mg/kg IV.^{170 172}

Infants: Inject 0.05 mg IV initially, repeated at 20- to 30-minute intervals as needed.^{170 172}

Sensitivity Reactions

Anaphylaxis

IM

Inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection) (up to 0.5 mg/dose), repeated every 10–20 minutes as needed for up to 3 consecutive doses.¹⁰¹

For self-administration using a prefilled auto-injector (e.g., EpiPen), inject 0.15 or 0.3 mg, depending on body weight; a dose of 0.01 mg/kg generally is recommended.¹⁶³ Clinicians may recommend higher or lower doses depending on individual patient needs and considering the life-threatening nature of anaphylaxis.¹⁶³ The 0.15-mg dose may be more approriate for children <30 kg.¹⁶³ If doses <0.15 mg are considered more appropriate, alternative injectable forms of the drug should be used.¹⁶³ For severe persistent anaphylaxis, repeated doses may be needed.¹⁶³

Sub-Q

Inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection) or 0.3 mg/m² (0.3 mL/m² of a 1:1000 injection) sub-Q.^{a 169} Single pediatric doses should not exceed 0.5 mg, repeated as needed at 20-minute to 4-hour intervals depending on the severity of the condition and the response of the patient.^{a 169}

IV

In severe anaphylactic shock, IV administration may be necessary since absorption may be impaired with sub-Q or IM administration.^{a 101}

If necessary, inject an initial dose of 10 mcg/kg (0.1 mL/kg of a 1:10,000 dilution), followed by a continuous IV infusion at an initial rate of 0.1 mcg/kg per minute (using a diluted solution containing 4 mcg/mL); the infusion may be increased as necessary to a maximum of 1.5 mcg/kg per minute to maintain BP.¹⁰¹

Neonates, alternatively: Inject 0.01 mg (10 mcg)/kg.^{170 172}

Infants, alternatively: Inject 0.05 mg (50 mcg) initially, repeated at 20- to 30-minute intervals as needed.^{170 172}

CPR and Cardiac Arrhythmias

Bradycardia and Pediatric Advanced Life Support

IV

Neonates: The usual dose is 0.01–0.03 mg/kg (0.1–0.3 mL/kg of a 1:10,000 injection),^d repeated every 3–5 minutes if necessary for CPR or bradycardia.^{a 161} Higher IV doses are not recommended^{161 d} because of risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function.^d

Pediatric Patients: The usual initial dose is 0.01 mg/kg (0.1 mL/kg of a 1:10,000 injection), up to a maximum single dose of 1 mg, for CPR or bradycardia,^{a 161 d e} repeated every 3–5 minutes as needed.^{161 d} Higher IV doses not recommended; use a standard dose for the first and subsequent doses.^d No survival benefit from routine use of high-dose epinephrine; may be harmful, particularly in asphyxia.^d Risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function with high doses.^d May consider high-dose epinephrine in certain circumstances (e.g., β-adrenergic blocking agent overdose).^d

Pediatric Patients: Alternatively, infuse at an initial rate of 0.1 mcg/kg per minute; increase the rate in increments of 0.1 mcg/kg per minute, if necessary, to a maximum of 1 mcg/kg per minute.^{a d} Low-dose infusions (<0.3 mcg/kg per minute) generally produce predominantly β-adrenergic effects,¹⁶¹ while higher-dose infusions (>0.3 mcg/kg per minute) generally result in α-adrenergic vasoconstriction, but there is substantial interindividual variation in catecholamine response, and infusion dosage should be titrated to the desired effect.^d

Pediatric patients: For refractory bradycardia, consider continuous infusion^d at a rate of 0.1–0.2 mcg/kg per minute.¹⁶¹

Intraosseous

Pediatric patients: The usual initial dose is 0.01 mg/kg (0.1 mL/kg of a 1:10,000 injection), up to a maximum single dose of 1 mg, for CPR or bradycardia,^{a 161 d e} repeated every 3–5 minutes as needed.^{161 d} Higher intraosseous doses are not recommended; use a standard dose for the first and subsequent doses.^d No survival benefit from routine use of high-dose epinephrine; may be harmful, particularly in asphyxia.^d Risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function with high doses.^d May consider high-dose epinephrine in certain circumstances (e.g., β-adrenergic blocking agent overdose).^d

Endotracheal

Optimum dose not established.^{a 161 d}

Neonates: IV administration (of 0.01–0.03 mg/kg per dose [0.1–0.3 mL/kg of a 1:10,000 injection])¹⁶¹ is the preferred route.^{a d} If the endotracheal route is used, doses of 0.01 or 0.03 mg/kg will likely be ineffective.^d Although safety and efficacy have not been established, consider endotracheal administration of a higher dose (up to 0.1 mg/kg) while access is being obtained.^{a d}

Pediatric patients: The usual initial dose is 0.1 mg/kg (0.1 mL/kg of a 1:1000 injection), up to a maximum single dose of 10 mg, for CPR or bradycardia,^{a 161 d e} repeated every 3–5 minutes as needed.^{161 d}

Generally flush the dose with a minimum of 5 mL of 0.9% sodium chloride injection followed by 5 assisted manual ventilations to promote absorption.^{161 a d}

Intracardiac

Pediatric patients: 0.005–0.01 mg/kg (0.05–0.1 mL/kg of a 1:10,000 injection).^a

Adults

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

220 mcg (1 inhalation) of epinephrine via an MDI, repeated once if necessary after at least 1 minute; do not administer subsequent doses for at least 3 hours.^{a 166}

After placing approximately 10 drops of 1% (1:100) epinephrine in the nebulizer reservoir, administer 1–3 deep inhalations via the hand-bulb.^{a 168} Do not repeat more often than every 3 hours; the least number of inhalations producing relief should be used.^{a 168}

Sub-Q

For severe asthma, the usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection).^a Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.^a

May give at 20-minute to 4-hours intervals depending on the severity of the condition and patient response.^a

Alternatively, may administer 0.01 mg/kg (concentration of 1:1000) divided into 3 doses of approximately 0.3 mg, given at 20-minute intervals.^{a d}

IM

For severe asthma, the usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection).^a Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.^a

IV

0.1–0.25 mg injected slowly.¹⁷⁰

Sensitivity Reactions

Anaphylaxis

IM

The usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection).^a

For the treatment of reactions caused by drugs that were given IM, epinephrine may be administered at the site of injection of the other drug to minimize further absorption.^a

Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.^a

Alternatively, inject 0.3–0.5 mg (0.3–0.5 mL of a 1:1000 injection),¹⁶¹ repeated every 15–20 minutes, as needed.^d

For self-administration using a prefilled auto-injector (e.g., EpiPen), inject 0.3 mg.¹⁶³ Clinicians may recommend higher or lower doses depending on individual patient needs and considering the life-threatening nature of anaphylaxis.¹⁶³

For severe persistent anaphylaxis, repeated doses may be needed.¹⁶³

Sub-Q

Consider the possibility that drug absorption from sub-Q injection may be inadequate in anaphylaxis, particularly with shock.^{161 d}

The usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection).^a For the treatment of reactions caused by drugs that were given sub-Q, epinephrine may be administered at the site of injection of the other drug to minimize further absorption.^a

Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.^a

May be given at 20-minute to 4-hours intervals depending on the severity of the condition and patient response.^a

Alternatively, inject 0.3–0.5 mg every 20 minutes as needed for up to 3 doses.^{160 162}

IV

In severe or life-threatening anaphylaxis, IV administration may be necessary since absorption may be impaired with sub-Q or IM administration.^{a 101 161 d}

If necessary, inject 0.1–0.25 mg^{a 161 172 d} (e.g., 1–2.5 mL of a 1:10,000 injection or dilution) slowly and cautiously (e.g., over 5–10 minutes), and repeat every 5–15 minutes as necessary or follow by a continuous infusion at an initial rate of 1 mcg/minute, increasing the rate to up to 4 mcg/minute as necessary.^{a 161 d} Individual doses up to 0.5 mg also have been used.¹⁶¹

To optimally control administration, some clinicians recommend an initial dose of 0.1 mg (10 mL of a 1:100,000 injection or dilution) given over 5–10 minutes, followed by a continuous infusion as necessary.¹⁰⁰

Alternatively, 0.025–0.05 mg (0.25–0.5 mL of a 1:10,000 injection) be given every 5–15 minutes following initial sub-Q or IM administration of 0.5 mg.^a

CPR and Cardiac Arrhythmias

The optimum dose of epinephrine during CPR remains controversial.^{103 104 115 116 117 118 119 120 121 122 123 125 126 127} The usual dose of 0.5–1 mg has been questioned since it is not based on body weight^{103 104 117 119 120} and may be lower than necessary for optimum cardiovascular effects.^{103 104 117 119 121 127}

CPR (Cardiac Arrest)

IV

Inject 1 mg every 3–5 minutes.^{161 d}

Has been infused at an initial rate of 1 mcg/minute and, increased to 3–4 mcg/minute as needed, via a central line to reduce the risk of extravasation and ensure good bioavailability.¹⁶¹

Higher (>1-mg) doses may be indicated in certain circumstances, (e.g., β-adrenergic or calcium-channel blocking agent overdose).^d

Intraosseous

Intraosseous doses generally are the same as those administered IV.^{a d}

Usually, 1 mg every 3–5 minutes.^d

Endotracheal

Optimum dose not established.^{a 161 d}

If IV or intraosseous access is delayed or cannot be established,^d endotracheal doses 2–2.5 times those administered IV (i.e., 2–2.5 mg) are recommended.^{a 161 d}

Intracardiac

Inject 0.1–1 mg (usually as 1–10 mL of a 1:10,000 injection) into the left ventricular chamber.^{a 161 170 172}

Sub-Q

Following initial IV administration, 0.3 mg may be injected sub-Q.^a

Persistent or Recurrent Ventricular Fibrillation/Tachycardia

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.^{161 d}

Pulseless Electrical Activity

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.^{161 d}

Asystole

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.^{161 d}

Bradycardia:

IV

For symptomatic bradycardia without cardiac arrest, infuse at an initial rate of 1 mcg/minute; subsequent dosage is adjusted according to the patient’s response and generally ranges from 2–10 mcg/minute.^{a 161 d}

Radiographic Use

Arteriography

IV

As an adjunct in arteriography†, 16–24 mL of sodium chloride injection containing 1 mcg of epinephrine per mL has been infused into the celiac or superior mesenteric artery† over 2 minutes; the radiographic contrast medium was administered 7–10 minutes later.

Hemorrhage

GI

Intra-arterial

To control GI bleeding†, infuse into the celiac artery†, inferior mesenteric artery†, or superior mesenteric artery† at a rate of 8–20 mcg/minute for 4 minutes to 3 hours.

Renal

Intra-arterial

To control bleeding from the kidney†, infuse into the renal artery† at a rate of 10 mcg/minute for 10 minutes.^a

Radiation Nephritis

Abdominal Irradiation

Intra-arterial

To prevent radiation nephritis†, infuse into the renal artery† at a rate of 3–7.6 mcg/minute for 4–10 minutes prior to and continued during the period of abdominal irradiation.^a

Adjunct to Local Anesthesia

Local Injection

To localize and prolong the duration of local anesthesia, epinephrine may be used in concentrations of 1:500,000 to 1:50,000; 1:200,000 is used most commonly.^{a 172}

Superfic