Have You Ever Used an EpiPen Before?

Ut oh, his lips and face were already swollen.

"Hey man, my name's Dean, I'm one of the paramedics. Have you ever used an EpiPen before?" The patient nodded his head. "Great, this is sorta like that. Same medicine."

I drew up 0.3 mg of epi and administered it IM.

The patient was a 17-year-old high school kid who was in the school cafeteria when he was exposed to peanuts. His friend forgot about his allergy and brought a PB&J... Whoops.

"That should kick in a few minutes," he nodded again, "in the meantime, let's get you on the stretcher."

Fire helped us pick him up and loaded him in the ambulance - he was already starting to look better.

When we first got on scene this kid looked terrible. He was SOB, wheezing, and tachycardic, and he had a pronounced, blotchy, erythematous rash on his face/neck that led to his swollen lips and chin. He was flush, anxious, and looked terrified. I didn't even have to hear his muffled, constricted voice to know he needed some epi.

This kid had an obvious anaphylactic reaction to peanuts. I could tell he needed epi while walking up to the scene.

Anaphylaxis is a severe, life-threatening hypersensitivity reaction. Specifically, it's a type-I hypersensitivity reaction that is IgE-mediated. IgE is a type of antibody. Without getting too lost in the weeds here, an allergy is a hypersensitivity reaction to an otherwise harmless substance. A true anaphylactic reaction requires prior sensitization. Here, the body decides it doesn't like something and creates antibodies against it. The next time you are exposed to that substance, antibodies recognize it and initiate this chain of events to ultimately try to get rid of it.

This "try to get rid of it" part is less than pleasant for the body…

This kid was sick. He had the works: Hives, swelling, bronchospasm/SOB, GI upset w/ nausea and vomiting... I assume hypotension too, but I didn't wait to find that part. We had all we needed to make the diagnosis.

There are a few different clinical criteria that need to be met to call something "anaphylactic" vs just an allergy. The most common criteria, at least in the region I work in, requires two or more of the following with rapid progression following exposure to an antigen: (1) Skin/mucosal involvement, (2) respiratory compromise, (3) hypotension, and (4) persistent GI symptoms.

This patient had (1), (2), and (4) at least. He may have had hypotension too, to be fair, but usually, airway/GI symptoms predominate food-related reactions.

The onset of anaphylaxis is usually < 30 minutes from exposure, but it can be later. It all starts with mast cells. IgE receptors on mast cells bind to antigens which causes the mast cell to degranulate (think: exploding balls of histamine). Histamine is the main culprit here, but there are other chemicals involved too. These are inflammatory mediators that set off a chain reaction in the body.

These mediators are responsible for four main events: (1) Chemotaxis, (2) smooth muscle constriction in the airways, (3) smooth muscle constriction of the GI tract, and (4) vasodilation/increased vascular permeability.

Chemotaxis is a rallying of the troops. Here there is a release of different mediators that call other WBCs, etc. to the area. These all release more and more histamine and perpetuate the reaction.

The histamine that is released causes smooth muscle constriction. Namely, it causes smooth muscle constriction in the airways and GI tract. In the airways, this leads to bronchospasm, wheezing, shortness of breath, hypoxemia, stridor, etc. This tends to be much worse in patients with pre-existing asthma. In the GI tract, this leads to GI upset and nausea, vomiting, and diarrhea. This is often a forgotten criteria for anaphylaxis, esp. in food allergies.

Vasodilation and increased vascular permeability cause the angioedema and hypotension that can be seen in anaphylaxis. Angioedema is swelling in the deeper dermis/subcutaneous tissues of the skin. Both urticaria (hives) and angioedema are due to the release of histamine from cutaneous (skin) mast cells and are closely related to vascular permeability issues (leaking capillaries).

Food is the most common cause of outpatient anaphylaxis, making up around 1/3 of all outpatient cases - the ones EMS deals with. 90% of all outpatient anaphylaxis-related deaths are due to peanuts and tree nuts - a terrifying statistic.

The big jam with anaphylaxis is airway compromise and shock.

Anaphylaxis can cause a form of distributed shock due to inflammatory-mediated vasodilation and increased vascular permeability. This is bad, but the airway problems are probably worse - Airway collapse is the principal cause of death from anaphylaxis.

We need to inspect these patient's airways very carefully. We technically can't see if the larynx is swollen, but we can see the uvula.. this may indicate laryngeal edema. Stealing a page out of ENT's techniques/literature, you can have the patient vocalize a high-pitch "E" sound - this brings the vocal cords very closely together, and thus, even a minor degree of laryngeal swelling should prevent the sound from being pronounced properly. If the patient is just sitting there breathing, you may miss this subtle sign. Also, be on the lookout for hoarseness, complaints of lumps in the patient's throat, etc. - these can be ominous signs. This swelling is often paired with wheezing, etc. too.

But enough patho, S/S, etc. - Let's talk treatment.

First and foremost, if possible, stop the continued exposure to the antigen. This could mean pulling the stinger out, removing the patient from the cafe at school, etc. Stop the source of the reaction.

The next most important intervention is giving epinephrine. Give epi, 0.3-0.5 mg (in adults) IM in a big muscle group. EpiPen, just drawing it out of vial - whatever. Give epi. The earlier epi is administered, the better. Epi can fix both the respiratory components and the circulatory issues. It also stops histamine release somewhat directly. Remember, epi is both a beta drug and an alpha drug. Epi will inhibit mast cell degranulation and cause bronchodilation while also causing vasoconstriction, which reduces the vascular tone and improves preload - addressing the distributive shock.

I like to give epi early and aggressively in the lateral thigh. The dose of epi should cause pretty rapid improvement, but if it doesn't, hit them with it again. If it still doesn't, hang an epi drip.

Other interventions include O2, volume expansion with crystalloids, antihistamines, bronchodilators, and corticosteroids... These calls can get busy. But to me, none of these things should come before epi. The treatment of anaphylaxis is epi, epi, epi, and more epi, than everything else.

O2 can be administered via NC, NRB, or ETT. Anaphylaxis can cause profound V/Q mismatch and airway obstruction. If swelling progresses or if it doesn't improve with epi, intubation should be considered if you have the means to do so. But keep in mind, intubation is an absolute last resort... The patient will attempt to compensate for airway narrowing by self-treating resistance - the vent and ETT won't and RSI drugs abolish that compensation.

Volume can be important for these folks. These patients tend to respond well to 1-2 L of saline - but watch for pre-existing conditions that could complicate that.

Antihistamines (diphenhydramine, mainly) should NEVER delay epi... but are important nonetheless. H1 receptors mediate a bunch of the histamine problems. Antihistamines compete with histamine on their binding sites. These drugs do not get rid of the mediators - an important distinction.

Bronchospasm can be treated with a standard nebulizer like albuterol. Keep in mind that epi is a med for this one too.

Finally, corticosteroids. These drugs lack evidence but are associated with a decrease in angioedema resolution. Corticosteroids alter inflammation directly and work via a variety of mechanisms.

With that said, and I can't stress this enough, EPI. Give EPI. I have never regretted giving epi to these patients - but I have regretted NOT doing it, for what it's worth.

So with that said, this kid got epi.

Once we were in the ambulance I placed him on some O2 and set up for an IV while my partner got to the front of the truck to drive to the closest hospital (a regional, moderately-sized hospital). En route I started him on a neb, gave him some diphenhydramine, some solu-cortef, and then ultimately another epi when he began to speak with a hoarse voice again.

By the time we got to the hospital, he was finally improving. He could speak in half sentences, his swelling was going down, and he stated his throat was feeling better. He didn't vomit after that either, which was a plus.

He was discharged around 10 hours later... Pretty cool, huh? I've always loved these calls because these patients can be SO sick, these calls are so busy, and yet, after a bunch of EMS interventions, they can get better and be discharged that day - essentially solely after what we did in the field and some observation. Thats cool. We pick these patients up on the brink of death and then drop them off FAR better than we met them.

What are your thoughts? Does your service carry EpiPens or just use epi drawn from a vial like mine? Have you ever seen a really sick anaphylactic patient? Tell me about it below! What did you learn from it?

Thanks for reading!

-Dean Stockley

References: 

Backer, DD. Ch. 28: Anaphylaxis and Anaphylactic Shock. Critical Care Medicine, 5th ed. Elsevier, 2019.

Zull, DN. Ch. 178: Anaphylaxis. Harwood-Nuss' Clinical Practice of Emergency Medicine, 7th ed. Wolters Kluwer, 2021.