Epinephrine


Article Author:
Rajeev Dalal


Article Editor:
Dejan Grujic


Editors In Chief:
Paul DiCesare


Managing Editors:
Frank Smeeks
Scott Dulebohn
Erin Hughes
Pritesh Sheth
Mark Pellegrini
James Hughes
Richard Ciresi
Phillip Hynes


Updated:
10/27/2018 12:31:33 PM

Indications

Epinephrine is one of the most commonly used agents in a variety of settings as it functions as medication and hormone. It is currently FDA-approved for various situations, including emergency treatment of type 1 hypersensitivity reactions including anaphylaxis, induction, and maintenance of mydriasis during intraocular surgeries, and hypotension due to septic shock. Off-label uses of epinephrine include, but are not limited to, ventricular fibrillation, pulseless ventricular tachycardia, asystole, pulseless electrical activity, croup, and severe asthma exacerbations unresponsive to standard treatment. In the operating room (OR) setting, epinephrine is used as a local anesthetic block as well. Produced by the adrenal medulla, epinephrine plays a vital role in the body’s acute stress response by stimulating the sympathetic nervous system.

Mechanism of Action

Epinephrine is a sympathomimetic catecholamine that exerts its pharmacologic effects on both alpha and beta-adrenergic receptors using a G protein-linked second messenger system. It has a greater affinity for beta receptors in small doses. However, large doses produce selective action on alpha receptors. Through its action on alpha-1 receptors, epinephrine induces increased vascular smooth muscle contraction, pupillary dilator muscle contraction, and intestinal sphincter muscle contraction. Other important effects include increasing heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production.

Administration

Depending on the diagnosis, epinephrine can be given in various forms. For the treatment of anaphylaxis, epinephrine is preferably injected intramuscularly into the anterolateral aspect of the thigh due to rapid absorption or subcutaneously as well. For advanced cardiovascular life support (ACLS), epinephrine may be given intravenously or intraosseous if needed. Another route of administration is through an endotracheal tube often used in neonatal resuscitation.

Adverse Effects

Adverse Effects Listed by System

  • Central nervous system (CNS): Anxiety, dizziness, nervousness, agitation, headache, Parkinson’s disease exacerbation
  • Cardiovascular: Arrhythmias, chest pain, hypertension, palpitations, tachycardia, cerebrovascular accidents, ventricular ectopy, vasospasm, tissue ischemia
  • Dermatologic: Gangrene at injection site (especially in buttocks), skin necrosis with extravasation
  • Endocrine: Hyperglycemia, hypokalemia, lactic acidosis
  • Gastrointestinal: Nausea, vomiting, increase in AST and ALT
  • Neuromuscular: Tremors, weakness
  • Renal: Decreased renal perfusion
  • Respiratory: Dyspnea, pulmonary edema

The more common side effects include tachycardia, hypertension, headache, anxiety, apprehension, palpitations, diaphoresis, nausea, vomiting, weakness, and tremors.

Drug Interactions

  • Alpha-adrenergic blockers: Antagonizes pressor effects
  • Antihypertensives: Antagonizes pressor effects
  • Vasodilators: Antagonizes pressor effects
  • Diuretics: Antagonizes pressor effects
  • Beta-adrenergic blockers: Potentiates pressor effects
  • Monoamine oxidase (MAO) inhibitors: Potentiates pressor effects
  • Catechol-o-methyltransferase (COMT) inhibitors: Potentiates pressor effects

Careful monitoring of vital signs is crucial especially in patients with polypharmacy.

Contraindications

There are no absolute contraindications against using epinephrine. Some relative contraindications include hypersensitivity to sympathomimetic drugs, closed-angle glaucoma, anesthesia with halothane. As is the case with prescribing any medication, all practitioners should use clinical judgment and evaluate the benefits versus risk with epinephrine.

The use of epinephrine in select circumstances must be assessed as discussed below.

Pregnancy

Epinephrine is considered a pregnancy Category C medication. There are no well-controlled studies in humans, although animal studies have shown a teratogenic risk during organogenesis. It is capable of crossing the placenta. Gastroschisis has been demonstrated when epinephrine has been administered subcutaneously in rabbits at 15 times the maximum dosage. Epinephrine should be used cautiously when maternal blood pressure is 130/80 mm Hg and greater.

Labor and Delivery

Due to its effect on beta-2 adrenergic receptors causing tocolysis, epinephrine opposes the actions of oxytocin on the uterus and may delay labor. It must also be used with caution during anaphylaxis induced hypotension in pregnancy as it may lead to uterine vasoconstriction, thus decreasing oxygen delivery to the fetus.

Breastfeeding

More clinical studies are needed to determine if epinephrine is excreted through breast milk.

Pediatrics

Epinephrine is effective at a dilution of 1:100,000 to 1:400,000 for mydriasis induction and maintenance in pediatric intraocular surgeries.

Geriatrics

Due to the expected decrease in renal, hepatic, and cardiac function of geriatric patients, epinephrine should be started at the lower end of the dosing regime and titrated appropriately for clinical effect.

Location

Several locations should be avoided when injecting epinephrine specifically the digits, nose, penis, and toes as these areas are more prone to ischemia. Epinephrine should be avoided in tissues supplied by end arteries.

Monitoring

When administered parenterally, epinephrine has a rapid onset, but short duration of action. When given intravenously, it has a half-life of fewer than 5 minutes. It is primarily metabolized in the liver along with various other locations such as the kidneys, skeletal muscle, and mesenteric organs. It is degraded into an inactive metabolite named vanillylmandelic acid by MAO and COMT and excreted into the urine. However, a small amount of the drug is excreted unchanged as well.

Epinephrine is a hormone that produces widespread effects. Certain effects need to be monitored. Tachycardia and hypertension are expected when epinephrine is given intravenously, so it is important to titrate carefully while monitoring hemodynamics. Epinephrine is also used with anesthetic agents to provide analgesia. In locations where extravasation of epinephrine has occurred, prevention and treatment of ischemia-induced necrosis are necessary. The infiltrated area should be treated with 10 mL to 15 mL saline solution containing 5 mL to 10 mg of phentolamine, an alpha-adrenergic blocking agent.

Renal impairment must be monitored as epinephrine causes renal blood vessel constriction and can decrease urine impairment. In patients with chronic kidney disease and various other renal pathologies, clinical judgment should be exercised. During intraocular use, epinephrine must be diluted otherwise corneal endothelial damage can result if undiluted concentrations of sodium bisulfite are administered.

Toxicity

Administration of excess epinephrine that leads to supra-therapeutic levels may cause predictable adverse effects that warrant supportive treatment. Overdose may cause elevated arterial pressures leading to cerebrovascular accidents. Pressor effects can be minimized by the usage of an alpha-adrenergic blocker or by the usage of vasodilators such as nitrites. Pulmonary edema has also been noted due to the underlying mechanism of peripheral vasoconstriction along with myocardial stimulation. Respiratory support may be needed alongside an alpha-adrenergic blocking drug to decrease vasoconstriction and enhance vascular flow. Due to strong beta-1 adrenergic effects on cardiac tissue, epinephrine toxicity may lead to potentially fatal cardiac arrhythmias or ischemia. Treatment involves administration of beta-adrenergic blocking agents such as metoprolol.


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Epinephrine - Questions

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Which of the following is not an indication for the use of epinephrine?



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A patient involved in a motor vehicle accident presents to the emergency department. After the appropriate protocol is initiated, the patient is evaluated for a laceration of a finger. The decision is made to inject epinephrine with bupivacaine prior to primary closure with sutures. Shortly thereafter, pallor of the finger is noted. Which of the following should be done?



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A patient with insulin-dependent diabetes mellitus presents with symptoms of dyspnea and wheezing. Beta-agonist treatment is initiated but fails to resolve the acute episode of dyspnea and wheezing. The patient is given epinephrine. Which complication is most likely?



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When injecting a local anesthetic with epinephrine, which of the following locations should be avoided?



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The addition of epinephrine to a local anesthetic has many desirable effects. Which effect is not seen with this combination?



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A patient is scheduled for same-day surgery. The anesthesiologist plans to use a local anesthetic such as lidocaine. What is the rationale for including epinephrine with the anesthetic?



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A 65-year-old female with a past medical history of coronary artery disease, type 2 diabetes mellitus, hypertension, and hyperlipidemia presents to the hospital with an extremely painful red eye and decreased vision. She states she notices halos around lights. The patient states this occurred very suddenly. She also complains of a headache. She states her mother had "some eye problem" but does not know what it was. Which of the following medications is contraindicated?



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During the resuscitation of an adult with symptomatic bradycardia, the code team requests an epinephrine infusion of 2 mcg/min. In the crash cart, a 1 mL vial of a 1:1000 epinephrine solution and a 500 mL bag of normal saline are found. Which of the following is true?



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A 65-year-old male is found at home febrile and unresponsive. He is brought to the emergency department. His blood pressure is 60/40 mmHg, pulse 45 beats/min, temperature 38.4C, and respiratory rate 22/min. Upon administering fluids, a physical exam is conducted. There is marked tenderness at the costovertebral angle. Urinalysis is positive for leukocyte esterase and WBCs. Which of the following is the best medication to resuscitate him?



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A 67-year-old male uses a topical preparation to control his open-angle glaucoma and subsequently experiences episodes of tachyarrhythmias. Which of the following is most likely to produce this effect?



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What is the primary reason the advanced cardiac life support protocol recommends epinephrine?



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Epinephrine synthesis is affected by which of the following enzymes?



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Which of the following is an adverse effect of administering the drug of choice in anaphylactic shock?



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Which of the following is the most likely consequence of the rapid administration of high-dose intravenous epinephrine?



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An 87-year-old female is found down in her bathroom by her daughter. After feeling no pulse and initiating the emergency medical services, CPR is performed. An ambulance arrives, and an automated external defibrillator reveals asystole. The appropriate medication is used. Which of the following physiologic effects is expected?



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What is the dose of epinephrine for neonatal resuscitation?



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A 6-year-old male accidentally ate a meal at school that exposed him to a substance to which he is allergic. He develops shortness of breath and quickly becomes hypotensive. What should be the route of administration of the most appropriate drug?



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A 12-year-old male is playing outside with his friends and is stung by a bee. He begins to feel lightheaded and has trouble breathing. What should patients be aware of regarding the use of an automatic epinephrine injector?



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Which of the following routes is not appropriate for administering epinephrine for the treatment of anaphylaxis?



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On which receptor does epinephrine have no action?



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The synthesis of epinephrine from norepinephrine requires which of the following?



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The action of epinephrine on beta receptors in the liver and muscle is that it stimulates which of the following?



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A 2-year-old presents to the emergency department with a barking cough, inspiratory stridor, and sternal wall retractions at rest. She appears minimally agitated. Racemic epinephrine is administered via a nebulizer. For how long is it appropriate to monitor this child for possible rebound of stridor?



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Epinephrine is used in treating numerous conditions. It exerts its actions by all of the following except what?



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An adult patient is emergently rushed to the hospital after being found down in his home. Appropriate ACLS protocol guidelines are initiated. The EKG shows ventricular fibrillation. What are the dose and the first drug of choice following two failed unsynchronized cardioversions?



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A 47-year-old male presents to the clinic with symptoms of episodic hypertension, palpitations, headaches, tachycardia, and sweating. His symptoms are not present at the time of examination. The metabolites of which of the following are most likely to be present following a 24-hour urine sample?



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Which of the following is true regarding the drug epinephrine? Select all that apply.



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Epinephrine - References

References

Update on the usage and safety of epinephrine auto-injectors, 2017., Posner LS,Camargo CA Jr,, Drug, healthcare and patient safety, 2017     [PubMed]
Insights into Pathophysiology from Medication-induced Tremor., Morgan JC,Kurek JA,Davis JL,Sethi KD,, Tremor and other hyperkinetic movements (New York, N.Y.), 2017     [PubMed]
Failure of Outpatient Management With Different Observation Times After Racemic Epinephrine for Croup., Smith N,Giordano K,Thompson A,DePiero A,, Clinical pediatrics, 2017 Oct 1     [PubMed]
Risk Factors of Vasopressor-Induced Symmetrical Peripheral Gangrene., Kwon JW,Hong MK,Park BY,, Annals of plastic surgery, 2018 Jan 9     [PubMed]
[Exposure to toxic dose of adrenaline on the functional state of the liver]., Kopylova SV,Vlasova KM,Anashkina AA,, Patologicheskaia fiziologiia i eksperimental'naia terapiia, 2017 Apr-Jun     [PubMed]
Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries- is epinephrine the culprit?, Jayamali WD,Herath HMMTB,Kulathunga A,, BMC cardiovascular disorders, 2017 Sep 4     [PubMed]

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