Reacting to Anaphylaxis

I recently gave an allergic reaction quiz based on local EMS protocols. When asked what first-line medication would be administered to a 15kg pediatric patient that has hives, rash, and wheezing, the majority answered diphenhydramine; even though protocol states to give epinephrine 1:1000 (EPI) intramuscularly (IM). In my opinion, there is a fear of pushing EPI IM based on the idea that EPI will potentially cause catastrophic cardiovascular events. Treating a sick child is a fear most of us have and may contribute to our hesitancy when administering potent medications such as EPI. Many believe diphenhydramine and albuterol are safer and can improve the allergic reaction before EPI is required.

In a retroactive study done in Broward County, Florida, only 15% of patients experiencing anaphylaxis were given EPI by the first responding paramedic. Of all the patients experiencing anaphylaxis, 48.1% received oxygen, 15.4% received EPI, 11.5% received IV fluids, 19.2% received albuterol, 25% received methylprednisolone, and 80.8% received diphenhydramine. In another study, only 36% of pediatric patients experiencing an anaphylactic reaction received EPI by EMS. In a cohort study in the United Kingdom looking at fatal anaphylactic reactions, the median time to respiratory/cardiac arrest was 30 minutes for foods, 15 minutes for venom, and 5 minutes for iatrogenic reactions. In these deaths, only 14% received EPI prior to arrest. These studies demonstrate that EPI is being under-utilized by EMS.

It is estimated that there are 5.9 million children under the age of 18 that have some kind of food allergy. That equates to 1 in every 13 children. More than likely, you personally will treat a pediatric patient experiencing an allergic reaction that meets the anaphylactic diagnosing criteria at some point in your career. The World Allergy Organization anaphylaxis criteria is as follows:

The fact of the matter is the first-line drug for anaphylaxis is EPI 1:1000. EPI is a mixed alpha and beta adrenergic agonist that works on multiple systems in the body; reducing or stopping the effects of anaphylaxis. The alpha properties reverse peripheral vasodilation, reduce hypotension, and assist in reducing angioedema, urticaria, and erythema. The beta properties reverse bronchoconstriction, increase cardiac contractility and output, and reduce the release of inflammatory mediators from the mast and basophil cells. There are no contraindications when administering EPI for anaphylaxis. Additionally, adverse cardiovascular events when administering via IM are low. In one study, 362 doses of EPI were given to 301 people having an anaphylactic reaction. Though 3 out of 30 people that received EPI IV developed cardiac complications, only 4 out of 316 (1%) who received EPI IM experienced the same adverse effects. Overdose occurred in 4 patients that received EPI IV compared to 0 in the patients that received it via IM. This evidence shows that IM is the safest and preferred route. IV administration should be a last resort in those who have not responded to multiple doses of IM injection or are experiencing cardiac/respiratory arrest.

What is the standard dose of EPI, and how do we give it IM? The automatic EPI pens come in 2 doses: 0.15mg (25kg or less) and 0.3mg  (>25kg). If utilizing a 1:1000 vial, the pediatric dose is 0.01mg/kg to a max of 0.3mg, and the adult dose is 0.3mg. Correctly performing drug calculations in a high stress situation increases likelihood of error. Fortunately, the pediatric dosing for EPI 1:1000 is as easy as moving the decimal 2 places to the left. Here is an example:

What is the preferred injection site for EPI IM administration? The preferred location is the vastus lateralis muscle or the lateral mid-thigh. The thigh muscle is a very thick vascular muscle and has a higher absorption rate. Additionally, there is a quicker rise of epinephrine plasma levels when compared to EPI given subcutaneously or in the upper arm.                                                                                                              

In summary, EPI is the first-line treatment for anaphylaxis, and it is underused. The American College of Allergy, Asthma and Immunology recognize this fact and have compiled a panel of expert allergist and emergency physicians to address this problem. They recommend emphasis be placed on the following key points:

• Appropriately dosed epinephrine is safe, and there are no absolute contraindications for its use in treating anaphylaxis.

• Delay in administration of epinephrine may lead to more severe and treatment-resistant anaphylaxis.

• Epinephrine administration is not only indicated for use in anaphylaxis, but also for severe allergic reactions and for patients identified as being at risk for anaphylaxis.

• Use epinephrine as the first-line therapy for anaphylaxis, for severe allergic reactions, and for mild symptoms following a suspected exposure to a trigger that has previously caused a serious allergic reaction.

• When in doubt, administer epinephrine!

I end this blog with a quote from Jay M. Portnoy, MD from the University of Missouri and Mercy Children’s Hospital: “Epinephrine is the first treatment — not [diphenhydramine], not steroids — because epinephrine works fast and reverses the anaphylactic reaction in about 30 seconds. [Diphenhydramine] doesn’t work for…almost an hour. For some reason, people are afraid to use it, perhaps because it is an injection, but they shouldn’t be because it is the treatment of choice. Why wouldn’t you use the 30 second drug if a patient is having a life-threatening reaction?”

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American Academy of Allergy Asthma & Immunology. (2014). Anaphylaxis- Treatment with Epinephrine IM Safer Than IV.  Retrieved from https://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/anaphylaxis-im-epinephrine

American Academy of Allergy Asthma & Immunology. (2015). Lateral Thigh Epinephrine. Retrieved from http://www.aaaai.org/ask-the-expert/lateral-thigh-epinephrine

Fare Allergy Research & Education. (n.d.). Facts and Statistics. Retrieved from, https://www.foodallergy.org/life-with-food-allergies/food-allergy-101/facts-and-statistics

Fineman, S.M., Bowman, S.H., Campbell, R L., Dowling, P., O’Rourke, D., Russell, S.C., Sublet, J.W., Wallace, D. (2015). Addressing barriers to emergency anaphylaxis care: from emergency medical services to emergency department to outpatient follow-up. Annals of Allergy, Asthma & Immunology, 115(4), 301-305. Doi.org/10.1016/j.anai.2015.07.008

Kemp, S.F., Lockey, R.F., Simons, F.E.R., World Allergy Organiztion ad hoc Committee on Epinepherine in Anaphylaxis. (2008).  Epinephrine: The Drug of Choice for Anaphylaxis–A Statement of the World Allergy Organization. World Allergy Organization Journal. 1(2). S18. doi.org/101186/2939-4554-1-S2-S18

Lowry, F. (2012). Paramedics Often Fail to Give Epinephrine for Anaphylaxis. Medscape. Retrieved from https://www.medscape.com/viewarticle/774828

Tiyyagura, G.K., Arnold, L., Cone, C.C., Langhan, M.  (2013) Pediatric Anaphylaxis Management in the Prehospital Setting, Prehospital Emergency Care, 18:1, 46-51, DOI:  10.3109/10903127.2013,825352

Waserman, S., Chad, Z., Francoer, M.J., Small, P., Stark, D., Vander Leed, T.K., Kaplan, A., Kastner, M. (2010). Management of anaphylaxis in primary care: Canadian expert consensus recommendations. Allergy, 65(9), 1082-92. doi: 10.1111/j.1398-9995.2010.02418.x.

Wood, J. P., Traub, S. J., & Lipinski, C. (2013). Safety of epinephrine for anaphylaxis in the emergency setting. World Journal of Emergency Medicine, 4(4), 245–251. doi.org/10.5847/wjem.j.issn.1920-8642.2013.04.001