Anaphylaxis is the rapid onset of an allergic reaction that is very serious and can cause death. Generally, the management to overcome this condition has the same procedure. However, there are different factors in each case, such as age, gender, to accompanying diseases. The Guideline of the American Academy of Allergy, Asthma & Immunology (AAAAI) clearly states that IM's epinephrine administration in treating anaphylaxis is the most recommended therapy. Administration of epinephrine by IM will result in peak concentrations in plasma, which are quite fast compared to administration by subcutaneous (SC), both in children and adults.


Safety of Epinephrine Administration in Anaphylaxis Treatment




On the other hand, antihistamines and corticosteroids are not recommended for first-line treatment of anaphylaxis. In allergic reactions, antihistamines, such as diphenhydramine, require a more extended mechanism of action and require a slower time to reach their peak compared to epinephrine. One study showed that antihistamines to reduce 50% of allergy symptoms after administration, took 52 minutes for diphenhydramine IM, 80 minutes for diphenhydramine orally, up to 101 minutes fexofenadine. Meanwhile, to overcome a fatal anaphylactic reaction, it takes less than 5 minutes since someone is exposed to allergens. Therefore, the use of antihistamines is not recommended to treat anaphylaxis.

Likewise, corticosteroids require a slower working time, so it is not recommended for treatment in anaphylactic conditions. Corticosteroids can prevent allergic events recurrence, so they are given as additional or advanced therapy, which can be given after epinephrine administration. Giving antihistamines and corticosteroids controls the clinical manifestations of allergic skin and cardiovascular, such as itching, urticaria, angioedema, and symptoms of the nose and eyes. Also, to prevent the recurrence of allergic events.


Dosage and Method of  Epinephrine Administration in the Anaphylaxis Treatment

Appropriate management of anaphylaxis is giving epinephrine injection IM (usually in the vastus lateral area) immediately. The dose is 0.01 mg / Kg weight (from a 1: 1,000 or 1 mg / mL epinephrine solution), the maximum dose of 0.5 mg at adults and 0.3 mg in children. The dose of epinephrine injection can be repeated every 5-15 minutes, as needed. Most patients require 1 to 2 times the dose of IM epinephrine injection. However, sometimes giving more than two times the dose can occur.

Intravenous administration of epinephrine can be considered, especially for severe hypotension cases, patients with cardiac and respiratory arrest, or patients who do not respond after repeated IM injections. Epinephrine infusion can be prepared by adding 1 mg (1 mL) 1: 1,000 ratio epinephrine to 250 mL of 5% dextrose solution to reach a concentration of 4 µg / mL. This 1: 250,000 liquid is then given at a rate of 1 mcg/minute (15 drops/minute with microdroplets), which can be increased according to the hemodynamic response, up to a maximum of 10 mcg/minute in adolescent and adult patients. It is safer to administer this epinephrine infusion using an infusion pump.


Factors causing dosing errors of epinephrine

Factors that can lead to dose errors in the administration of epinephrine, especially in the anaphylaxis treatment, include:
  • Lack of doctor's knowledge about the proper dosage and method of epinephrine administration in handling anaphylactic cases
  • The absence of clear labeling distinguishes epinephrine ampules between 1: 1,000 and 1: 10,000, which results in inaccurate dosing.
  • Store both epinephrine solutions in the same place, especially if the drugs are stored in alphabetical order.
  • Difficulty in calculating doses involving decimal numbers and epinephrine dose ratios.
  • Lack of communication between doctors and nurses is regarding epinephrine or the ratio of epinephrine dose used.

One study found that 94% of pediatric emergency physicians who were able to identify anaphylactic cases and provide epinephrine as their preferred management, only 67% of them gave epinephrine by IM probably since there are still many doctors who are not used to using epinephrine as the main therapy to their doubts about the safety of using epinephrine in anaphylactic cases.


Safety of Epinephrine Administration in Anaphylactic Treatment

Overdoses and cardiovascular side effects can occur with epinephrine administration. However, these overdoses and side effects usually appear more often in IV administration than IM.

A cohort study of 573 patients, of which 301 patients received at least one dose of epinephrine showed that of the 362 epinephrine doses given, 67.7% were IM auto injections, 19.6% were IM injections, 8.3% SC injections, 3.3% IV bolus injections, and 1.1% IV infusions. Moreover, it was found that the administration of epinephrine overdose occurred in 4 patients, and all were given by IV bolus injection. In contrast, cardiovascular side effects appeared in 3 patients from 30 doses of IV bolus injection (10%) than four patients out of 316 doses given IM (1.3%). Therefore, IV administration of epinephrine in anaphylactic cases must be seriously considered, given the cardiovascular side effects.

The intramuscular injection of epinephrine administration is safe for anaphylaxis, but it requires doctors and medical workers' skills to minimize dosage errors and drug administration methods. Essential points to improve the safety of using epinephrine in anaphylaxis management are:
  • Epinephrine is the first-line treatment of anaphylaxis, while antihistamines and corticosteroids are adjunctive therapies.
  • Epinephrine for the management of anaphylaxis must be given intramuscularly and not intravenously. Administration of intravenous epinephrine only when indicated.
  • The epinephrine in anaphylaxis treatment is  1: 1,000 concentration epinephrine solution, not  1: 10,000 epinephrine solution.

References
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2. Simons FE, Ardusso LR, et al. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis. WAO Journal. 2011; 4: p.13–37. downloaded from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500036/
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4. Campbell RL, Bellolio MF, et al. Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine. The Journal of Allergy and Clinical Immunology: In Practice. 2015; 3 (1): p. 76-80. downloaded fromhttps://www.sciencedirect.com/science/article/abs/pii/S2213219814002669?via%3
5. Farzam K dan Lakhar AD. Adrenergic Drugs.  downloaded from: https://www.ncbi.nlm.nih.gov/books/NBK534230/
6. Lieberman P, Nicklas RA, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010; 126 (3): p. 477–80.e42. downloaded from: https://www.jacionline.org/article/S0091-6749(10)01004-3/fulltext

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