Welcome to the third episode of the “Allergy, Asthma & Immunology Innovations Podcast.” This podcast episode is “What is anaphylaxis, and when to use epinephrine?” It examines how and why anaphylaxis happens, the symptoms that suggest you should administer epinephrine, potential side effects, and whether you should always carry two epinephrine devices.

The podcast is a collaboration between Allergy & Asthma Network and The Itch Podcast. It’s hosted by The Itch Podcast’s Kortney Kwong Hing and allergist/immunologist Payel Gupta, MD. In this episode, Kortney and Dr. Gupta are joined by David Golden, MD, a board-certified allergist and immunologist in Owings Mills, Maryland.

Allergy & Asthma Network thanks Aquestive for their sponsorship of this podcast.

You can listen to or download the podcast on ItchPodcast.com for listening anytime, anywhere. The podcast can be downloaded at:

Timestamp overview

  • 3:02 – Starting off with the basics: what is anaphylaxis?
  • 4:50 – When to use epinephrine?
  • 7:00 – How to know if your symptoms are anaphylaxis?
  • 8:02 – Side effects of epinephrine, and why side effects are a good thing
  • 12:03 – Do you have to go to the hospital after using epinephrine?
  • 14:40 – How anaphylaxis occurs and the role of histamine
  • 19:37 – Epinephrine dosing
  • 22:08 – Should you carry two epinephrine devices?
  • 27:40 – Adolescents and why they hesitate to carry epinephrine

Full Transcript

Kortney Kwong Hing: You’re listening to The Itch, a podcast exploring all things allergy, asthma and immunology. I’m your co-host Kortney, a real-life allergy, asthma and eczema girl.

Payel Gupta, MD: And I’m your second host, Dr. Payel Gupta, a board-certified allergy, asthma and immunology doctor. Kortney and I hope to balance each other out so that we get you all the information that you want and need about allergies, asthma and immunology.

Kortney: Today we’re bringing you another episode in our Allergy, Asthma and Immunology Innovations podcast series in collaboration with the Allergy & Asthma Network. This is actually one of three episodes that will come out this year exploring anaphylaxis and epinephrine.

Dr. David Golden joins us to unpack anaphylaxis and why it’s so hard to define. We also talk about why epinephrine is the only way to treat an anaphylactic reaction and the confusion around antihistamines.

Finally, Dr. Golden also busts some myths around anaphylaxis and epinephrine use that I have been living with for 30-plus years.

Our original interview with Dr. Golden was full of golden nuggets and we’ve decided to bring it to you in three parts. The other two parts that will be coming out, we’re going to be discussing the new methods being developed to administer epinephrine, which is really interesting for our needle-shy listeners. And our final episode will explore the language of fear used to discuss anaphylaxis and what patients need to know about anxiety related to their allergies.

Before we jump in, we want to thank Aquestive for sponsoring this episode.

Welcome, Dr. Golden. Can you give us a quick intro of who you are and what led you to be with us today talking about epinephrine?

David Golden, MD: Well, thank you for having me. It’s my pleasure. And I have spent many years, decades, involved in research on specifically insect sting anaphylaxis and treatment. And that obviously leads me to have a lot of experience with anaphylaxis.

And in recent years I’ve especially become involved aside from the research and education in the areas that I’ve been involved in, now being involved in guidelines development with the Joint Task Force on Practice Parameters for allergy for the American College of Allergy, Asthma & Immunology and American Academy of Allergy, Asthma & Immunology.

Some of the work that I have really focused on is anaphylaxis and epinephrine treatment of anaphylaxis. I have also been involved indirectly in the development of some of these new products, and one in particular that I have served as a consultant for with Aquestive is for Anaphylm™.

But we will talk about a range of products that are in development and why it’s so interesting and so important to us and our patients.

Kortney: Great. Well, we’re very excited to have you here to talk to us today. So let’s start off with the basics. What is anaphylaxis?

Dr. Golden: You’d be surprised how difficult that has been to define. Anaphylaxis is usually thought of as a multisystem allergic reaction, but it doesn’t have to be multisystem. Again, this gets complicated, but it’s an allergic reaction that is usually sudden, coming on rapidly and has the potential to be dangerous and life-threatening. I guess that’s the closest I can come to defining anaphylaxis.

We define it, of course, in the manifestations. So when I say multisystem, that usually means that it’s going to involve the four major components we talk about: it involves the skin, like people developing itching and hives and swelling; or the airway where there’s swelling of the tongue or throat or breathing problems. It can involve the circulation, causing low blood pressure leading to unconsciousness in the most extreme case, or just lightheadedness or dizziness; and the GI tract, so cramps, nausea, vomiting, diarrhea actually can be part of anaphylaxis as well, regardless of whether it’s food or drug or a bee sting.

So anaphylaxis is thought to usually involve the skin and one of those others. But there are people who, for example, get stung by a bee and go into shock and become unconscious, but don’t develop hives or any other signs or symptoms, which is why anaphylaxis is not always so easy to recognize and diagnose and treat when it’s not classical.

Dr. Gupta: It’s difficult for us to define that for patients at times, too, and to help patients understand exactly when their epinephrine is important to use. But I think, generally speaking, we go with the rules of two, which is if there’s two systems involved, then you want to use your epinephrine device. And so the skin is usually involved, but then also other areas like the GI tract, the respiratory tract, and all of those kinds of things.

Dr. Golden: Maybe I should add when to use epinephrine is a huge question, actually, that patients ask us and that we are still trying to develop the best advice for. And a couple of interesting points that are in our latest guidelines that are in press to be published shortly is that you don’t have to meet the criteria or definition of anaphylaxis to be treated with epinephrine on the one hand. And treatment with epinephrine is not the definition of anaphylaxis. So they’re connected, but that’s not how we make the decision.

When people ask us when to use epinephrine, we talk about what reactions they’ve had in the past, what kind of things that they may develop. And we balance between as we will talk about wanting people to use epinephrine as early as possible versus not unnecessarily.

And a good example are patients who do have allergies. If I’m around a cat, I’m going to get itchy and cough and wheeze. Is that anaphylaxis? Should I use my epinephrine? No, I’m having an allergic reaction to the cat. I should get away from the cat and take my medicine for my allergies. So that’s an example of something that technically meets the criteria for anaphylaxis, but it isn’t. And again, this is another example of how tricky it can be.

Kortney: As someone who’s had anaphylaxis to multiple different types of food, I know that my experience has never followed the same path. So that’s really exciting to hear that you are going to be publishing that. Because as a patient who’s never used epinephrine but has ended up in an ambulance one too many times, this episode is really important for me to hear because I’m always very hesitant on using my epinephrine because of exactly what you mentioned.

Is it really an anaphylactic reaction? I also have OAS to a slew of foods, so I’m always questioning whether, ‘Oh, is it multisystem or is it just my pollen allergy and I accidentally ate some raw apple and it’s all coming together.’ So, it is a very complicated landscape for patients, and I can imagine for doctors, it’s even more challenging because every patient you meet is super different and their comprehension of what’s going on in their body is different.

Dr. Golden: You’ve touched on a very important point that I know we’ll be talking about, and that’s hesitation to use epinephrine. I totally understand that, and you’re right. As we were just saying, it’s hard to distinguish. But on the other hand, epinephrine is amazingly safe. The only downside of using the epinephrine when you’re not quite sure is, well, you’ve just used an expensive epinephrine device. But I’m trying to balance again the fact that we don’t like there are people who, out of fear, I’m sure, use epinephrine treatment 20 times a year, and for the most part, that’s probably not necessary for that individual, but I would still rather them do that than not use it when they should.

Dr. Gupta: Yes, and I think that that’s also true for parents with infants and children with a food allergy. And so, Dr. Golden, can you just quickly highlight for us what are the potential side effects to using epinephrine besides the cost factor for patients, just so that they understand the safety profile of this medication?

Dr. Golden: Well, maybe I’ll start by saying why we use epinephrine because it is the only treatment that works. There is nothing else that works. I’ve heard many times people say, ‘I took my antihistamine and I got better.’ You didn’t get better because of the antihistamine. You got better because you got better. Antihistamines take 30 to 60 minutes sometimes to work and that’s far too long to expect any benefit for acute anaphylaxis. Steroids take hours to work. Not appropriate. For acute treatment of anaphylaxis, there’s really only one thing that works, and that’s epinephrine.

It’s the only thing that can stop the histamine cells, mass cells and basophils from releasing histamine. It stops the reaction in its tracks, so it arrests an allergic reaction. No other treatment can do that. And then it counteracts. It blocks many of the effects of histamine and other factors on the organs, like breathing or circulation or skin. So it stops the reaction it treats and gets rid of the symptoms and signs that can cause the danger of anaphylaxis. And having said that, it’s the only thing that works. People ask me, well, does it always work? And the answer is yes, but it may not work if it’s given too late.

And there are rare cases where epinephrine is not fully effective. But one of the most common reasons that it may not be fully effective is just waiting too long to use it. So early use is critical, and that’s why if you’re really not sure, but you’ve had previous experiences with anaphylaxis that your doctor said should have been treated with epinephrine, then you should use your epinephrine. If you’re not sure, it’s probably better to use the epinephrine than to wait.

People say, ‘Well, I’ll wait and see if it gets worse.’ As I just said, if you wait and it gets worse, the epinephrine may not work. Remember that epinephrine doesn’t work in seconds. We typically say it takes in the range of 8-10 minutes for an epinephrine injection to work. So don’t wait too long, because then you’re going to have to wait longer for it to work, and it may not even fully work.

It does have side effects. And again, maybe I should point out that epinephrine, we talk about it as a drug or treatment. We all have epinephrine in our bodies. Adrenaline is another name for it. It’s a natural product of our adrenal glands, and the body responds to stress and danger in many ways, one of which is to release epinephrine more into your system, to rev you up and get you ready to fight, whether that’s literally in hunter-gatherer days fighting the saber-toothed tiger, or whether it’s your body fighting anaphylaxis. The side effects of epinephrine, what epinephrine does in our body, our natural epinephrine or injection, is to speed things up in a sense. It raises the blood pressure, it raises the heart rate, and makes your heart race.

It can make you shaky, it can give you a headache, it can cause some nausea. These are all natural effects and can be viewed as side effects. So, if your heart is racing, yes, that’s a side effect. The blood pressure will go up. But these are surprisingly not found to be dangerous. We don’t talk about not giving epinephrine to someone who’s a heart patient or even someone who recently had a heart attack or bypass surgery. Anaphylaxis is more dangerous to them or to anyone than epinephrine ever would be.

So there are some natural side effects. People don’t like taking epinephrine because they feel shaky, they feel the heart race, they may get a headache, but these are not dangerous side effects.

Kortney: My first anaphylactic reaction on my own, so without my parents involved, I was 19 and I decided not to use my epinephrine because I thought, if I use my epinephrine, I need to go to the hospital. And that’s literally the reason I did not use it. I was like, ‘Oh, I don’t want to go to the hospital.’ I ended up in an ambulance going to the hospital. So that was a terrible decision. But was this just something I constructed, or is there a reason why I thought if I use my epinephrine, I have to go to the hospital?

Dr. Golden: I assume that somebody told you that because that’s what people get told. And we, as allergists, as doctors have, unfortunately, I would say for many years, told people, if you use your epinephrine, you must call 911. You must go to the emergency room. Maybe we didn’t explain that well. It’s not because of the epinephrine. It’s because of the anaphylaxis that people should have medical supervision and possibly additional treatment. What if you need intravenous fluids or oxygen? Epinephrine is not always completely effective. Intravenous fluids especially are sometimes very important in children and adults to fully treat severe anaphylaxis.

So this is something everyone has probably heard, is that correct? Well, there’s another thing. We’ve seen a lot of publications in our allergy journals by experts in the field arguing that point. And in fact, that’s another thing you will find in the soon to be published updated anaphylaxis practice parameters is a recommendation and a chart, actually a table of things to consider about activating emergency medical services for anaphylaxis, whether or not you use the epinephrine.

Above all, we don’t want people, as you just said, to not use epinephrine because then they have to go to the emergency department. In fact, what our guidelines are saying, and this is based on – actually it goes back to the early COVID pandemic when there was concern about going to the emergency room because they were overloaded and because of exposures. So, there were interim guidelines published in 2021 that basically said if you use your epinephrine early and you get better and you stay better, you don’t need to call 911.

And in our post-pandemic era that has taken hold, we are now incorporating that into an actual recommendation that basically says that if you treat early and it works well and you stay well, then you don’t need to go to the emergency room. The important thing is to use epinephrine early so that it can work well, and you can stay well. Because if it’s not fully effective or symptoms start to come back, then you need to use epinephrine again and call 911.

Dr. Gupta: So, Dr. Golden, thank you so much for all of that. I wanted you to kind of reverse and talk a little bit more about the way the epinephrine works. And I think for our listeners that might end up being patients, I want to kind of dissect it out a little bit more. I know you mentioned the mass cells, the histamine, all of that. Can we just slow that down a little bit?

Dr. Golden: Sure. It goes back to, ‘What is anaphylaxis?’ Allergies in general are caused by specialized allergic antibodies. Most of our antibodies are there to help fight infections and things like that. But there are also a kind of antibodies – IgE antibodies – that some of us who have allergies genetically, we’re programmed to make these allergic antibodies against basically harmless things, whether it’s apples or grass pollen or cats. The body mistakenly recognizes them as a threat and makes these allergic antibodies. And the antibodies attach themselves to allergy cells, mass cells and basophils. And then these cells are now armed and dangerous.

So the next time that particle of food or cat or whatever comes into contact with that mass cell, it is able to link those allergic antibodies that are programmed for cat and linking of the allergic antibodies causes these mass cells to release immediately. Histamine is what most people know is the major factor in allergic reactions. But there are many other factors, some of which are released more slowly. Mostly it’s the immediate release of factors like histamine that is able to have the kind of effects we were talking about. If I give you an injection of histamine, then you will probably break out in an itchy rash in hives. You may get throat tightness or have trouble breathing. You may get a drop in blood pressure. So histamine is one of the factors that causes the reaction within your system.

And the body has no internal antidote. The body does break down histamine fairly rapidly actually, but the allergy cells keep releasing histamine. There’s a whole lot of allergy cells and histamine that can be released during an ongoing allergic reaction. So, any treatment that can stop that release of histamine and other factors is critical. Antihistamines do block histamine, at least partially, so they can relieve the itching and rash of hives. They’re just not powerful enough to counteract the histamine effect on the blood pressure, for example, to prevent shock. Or antihistamines don’t really relieve asthma very well, for example. So that’s another example of where antihistamines are really not the effective treatment for an airway disease.

So I go back to saying epinephrine is the only thing we know of that actually works to relieve or prevent the progression and development of the symptoms. They go back to the allergic antibodies.

So I should back up for a moment and say that currently it’s the only treatment. We are entering an era, a very exciting era, of potential other new treatments. We’re seeing research now on small molecules, treatments that medications that might be given as a pill that would pretty much shut down the mass cell and prevent it from releasing histamine. Then I could take this pill and go visit the cat and have no reaction or eat the food or get stung by a bee. But will a medicine like that work on demand like epinephrine does? If I’m having an allergic reaction, can I take this pill and will it work fast enough to shut it down? Well, no pill is going to work that fast. It has to get into your system faster.

But there will be – I believe, we’ll have to see how they play out – new treatments that may add to our repertoire of things. Again, right now, epinephrine is the only thing that can do the things that we were just talking about to prevent the allergic antibodies and these armed mass cells from releasing histamine.

Dr. Gupta: Yes, and I think it’s just important to mention that a lot of those side effects are actually part of the reason that epinephrine works. So it’s meant to kind of increase your heart rate. It’s meant to kind of get the blood flowing to the right areas that the histamine dies down.

Dr. Golden: I like what you were just saying. That is something that I often try to point out to patients, that the side effects are good. This is what epinephrine is supposed to do. We think of side effects as an unwanted effect of a treatment. These are wanted effects. I tell patients if you feel jittery or you get a headache, this tells you it’s working, this is what it’s supposed to do. These are the effects you want. This is how it reverses anaphylaxis.

Dr. Gupta: I also think it’s interesting because we have different dosing, they know that the 0.10 dose vs. 0.15 vs. 0.30 is for the adults. You have the 0.10 dose. People get really nervous when they can’t afford or get that covered. But in general, we’ve been using the 0.15 for years. It ties into, I think, the whole notion of this is dangerous now I’m giving my child too much, etc.

Dr. Golden: Let me comment on epinephrine dosing again, because people often hesitate or worry for the wrong reasons. First of all, how do we know what the right dose of epinephrine is? No one’s ever done that study, and I don’t know if or when it will ever get done. The dosing that we now use and recommend, it’s called empiric dosing, meaning we do it because we’ve always done it and we know it works. There’s no research that ever proved this is the right dose. If anything, there’s more danger in giving too little than giving too much. And that’s the approach that we’re now taking. Yes, the 0.10 milligram dose has been a wonderful thing to have on the market. It’s certainly appropriate for certain weight or age ranges.

And we make a point in the recommendations, in practice parameters and guidelines that the 0.15 milligram dose has been and continues to be totally appropriate for young children and infants. If you don’t have or can’t afford, or your insurance doesn’t cover the 0.10 milligram, the 0.15 milligram is fine. It’s what we have always used and we’d rather, like I said, use a little too much than too little. And we’re now seeing that in the research literature, looking at adult dosing as well.

There’s a recent research study suggesting actually there are two papers and I don’t know where this will go in the future, but we’re now seeing evidence that the most appropriate dose for teens and adults is most likely 0.5 milligrams. And I think this is part of why we talk about the need for a second dose. Oftentimes the need for a second dose is, first of all, because the first dose wasn’t high enough, and number two, because it does take 8-10 minutes and sometimes much longer for epinephrine injection to work. So whatever dose you give by the current injection routes, the reaction may build up faster than the epinephrine can work. Again, underscoring why it’s so important to give it early on.

The bottom line is, don’t be afraid of higher dosing, that we now feel the appropriate way to go. Don’t be afraid of giving a second dose if necessary. Again, the danger is not giving it.

Dr. Gupta: So can we talk a little bit about carrying two epinephrine devices at once? And how do you make that recommendation on who should and shouldn’t carry two devices at all times?

Dr. Golden: I don’t know if it’s always the best recommendation for every patient. We really try to individualize that the actual frequency of needing a second dose is actually relatively low. It’s only for the most severe reactions, or if people delay and don’t use it early enough, that may lead to a need for a second dose. So I think my best answer is that people should have this discussion with their allergist and consider the pros and cons of the cost and need and benefit of having multiple epinephrine injectors.

We don’t think everyone necessarily has to have two at all times. There are people who clearly should. I’m going to sound like a broken record, but I believe that if we had people less fearful of using it and using it early at the correct dose, that the need for a second dose would be very uncommon. But if you need a second dose, you want to have it.

I’m just hedging a little to communicate that people, not everyone has the most severe type of anaphylaxis and using it for mild to moderate reactions is appropriate so that it won’t get more severe. But most people actually have a fairly consistent pattern of reaction. It may be a little more or less severe because, how much did you eat or how heavy was the exposure, or is your resistance lower for some other reason?

For most types of allergies, and I’ll put an exception on children with food allergies, but for most kinds of anaphylactic reactions, getting worse with every reaction is the exception, not the rule. So I can’t tell you how many times I’ve had patients who heard from the emergency room doctor, their primary doctor, and all their friends and relatives that the next one will kill you.

Actually, there are statistics on that and the chance of the next one killing you is about one in 300,000 to one in 500,000. So the fear of death, I can’t complain if it motivates people to use their epinephrine early, but I really hate people to have that anxiety that they’re going to die. The main reason to use epinephrine is to make that reaction go away faster and not be as severe and hopefully not need emergency room attention using it to prevent death, if that was the only reason you were using it. I hate to say it, but I’d have to point out that mortality from anaphylaxis is 0.1%.

The balance is trying to make sure people understand that it is the only thing that works, that taking antihistamines and waiting to see if you get worse is a very bad idea. That’s the real message.

I think the availability of more than one dose is important. I think we’re going to continue to see that in the way epinephrine products are packaged and recommended, because in reality, you never know whether this reaction is going to need a second dose. Maybe you couldn’t use your epinephrine right away and it’s going to get worse. As I was saying, higher doses are more uniformly effective unless we see epinephrine products with a higher dose. And there are other countries and other products in the world that do deliver 0.5 milligrams, for example, and there might be in the future higher dose products that some patients may get prescribed where having a second dose would be far less likely to be needed.

But currently what we have and what we’re likely to have in the coming years, I would like people to understand that in most circumstances and if they use it quickly, that they’re unlikely to need a second dose. The statistics are clear that it’s not a large number of people who need second doses. It’s actually 10% or less.

But what if you do? You need to have that available. Which is why, incidentally, we talk about stock epinephrine in the schools and on airplanes. There have been cost effectiveness studies showing that it would be better for every school to have three epinephrine devices and no child has to bring an epinephrine device to school. If the school had three devices, and if one got used, then that family would replace it. But it’s crazy to have 1,000 epinephrine devices in a school – talk about cost effectiveness.

So there are many different aspects we’ve looked at for the best way to make epinephrine available, widely available, rapidly available, and more acceptable to use to patients.

Dr. Gupta: Even having one available obviously is better than none. So it’s always a discussion that I have, especially with my adolescent patients that are like, ‘Oh my God, now you want me to carry around two of these things that I don’t want to carry around.’ You know, the message is always, like you said, Dr. Golden, you tailor it to each patient and what their kind of hesitancy is. That’s why it’s so important to discuss with your patients why they’re not carrying around what you want them to carry around.

And then I also wanted to just point out that the adolescent group – and I’m interested in those papers that you were talking about, Dr. Golden, on adolescents maybe needing higher doses. I wonder if it is because they’re delaying their use of the epinephrine and that’s why the studies show that they may need higher doses. I’m just curious, but I’m not sure. But in general, they are the highest risk population that we have because of their more risk-taking behaviors, lack of interest sometimes in carrying around their device, and just overall hesitancy towards administering the epinephrine when they feel the symptoms or are feeling sick.

Dr. Golden: Yes, that’s so true. The adolescents – I’ve always felt that age 14 is the highest risk age of all. I think that’s probably pretty close. And yes, there are multiple factors. So that’s a negotiation that we have and an important discussion. It’s important for us to have that communication with our patients so that we can have that discussion, and that if we’re good at it. This is the Shared Decision-Making that we talk so much about as far as understanding the patient’s values and preferences and then working with those and around those to get optimal care. So, we need to understand why they don’t want to carry it, why they don’t want to use it, and then see what we can do to mitigate that if they’ll carry one and use it right away.

Kortney: Thanks for listening. If you want to catch our next two episodes on anaphylaxis and epinephrine, make sure to subscribe to the podcast. And if you liked this episode, please share it amongst your friends and family to help create more awareness around these sometimes very confusing topics.

Again, thank you to our sponsor, Aquestive. If you want to learn more about what they’re doing to help make epinephrine a needle-free treatment, check out the links in our show notes.

Dr. Gupta: Thank you for listening to today’s episode. Remember that all information you hear today is for informational purposes only and are not intended to serve as a substitute for the consultation, diagnosis, and or medical treatment of a qualified physician or healthcare provider. And also, don’t forget to subscribe to our podcast.

And if you have a second, help spread the word by rating our podcast and sharing with your friends and family who might also be interested in learning more about allergies, asthma and immunology. You can always stay up to date by checking out our Instagram, the Itch Podcast, where you can leave questions you are itching to know, or check out our website, which is ItchPodcast.com, which contains more information about the subjects we covered in today’s episode and every episode. Until next time, have a fabulous week.