One of the nerve-racking parts of living with severe allergies is having to make the call about if and when an allergic reaction is anaphylaxis. A shot of epinephrine can save a life, but having to inject ourselves or our child with a needle is something we did not sign up for.

However, mistakes in the critical areas of recognizing and responding to anaphylaxis can mean the difference between life and death. Plus, studies are showing that prompt administration of epinephrine can simply reduce the chance that a food allergy reaction moves from relatively mild to severe anaphylaxis.

Over the years, Allergic Living readers have raised many questions related to epinephrine: from when to give it, to when a person needs a second dose, to issues such as how much heat or cold an epinephrine auto-injector can take, whether antihistamines mask anaphylaxis symptoms and more.

We asked Gina Clowes, the nationally known food allergy educator and parenting coach and consultant at AllergyMoms.com, to help us create a go-to epinephrine resource with answers to these vital questions.

Ginareached out to Dr. Julie Brown, anemergency medicine physician at Seattle Childrens Hospital, for her expertiseon the topic. Dr. Brown works closely with the food allergy community and has acontinuing research interest in epinephrine, auto-injectors and anaphylaxis. AsGina says, Were so grateful to Dr. Brown for agreeing to answer commonepinephrine questions. I find her insights and answers fascinating, and knowtheyll be helpful to a lot of people.

Following you will find written answers about epinephrine in a handy Q&A format. Plus, we include a podcast featuring Gina and Dr. Brown that offers further elaboration on some of the key answers.

Allergic Livings Epinephrine Q&A

Dr. Brown explained that epinephrine is adrenaline, the same hormone that is formed in the body in the fight or flight response. But it also has a very important role, probably by design, in turning off allergic reactions.

In the allergy context, she says epinephrine acts on a number of different receptors on cells in the body, and seems to reverse fairly pointedly all of the things that are happening in allergic reactions.

The reason is, the earlier you give epinephrine, the better outcomes are, says Dr. Brown. The longer one waits, the more likely the reaction is to progress and require multiple doses of epinephrine.

If we wait, were more likely to get sicker and have much more significant symptoms, she says. We are more likely to need multiple doses of epinephrine or need to stay in the hospital.

She reminds us that patients can start off having very mild symptoms, and then turn very quickly to getting very sick. What we want to do is to treat before things get serious. Sadly, most patients who have died from anaphylaxis had delayed treatment with epinephrine.

Dr. Brown generally recommends between 5 and 15 minutes as a reasonable timeframe between doses to determine if the epinephrine has taken effect. She says that if you have someone who looks like they are not breathing, they are turning blue, they are passed out, you would shorten the time window.

In such a case she says it may be reasonable to give a second dose, just to make sure that youve got a good amount of epinephrine circulating while awaiting an ambulance.

All About Epinephrine Podcast with Dr. Julie Brown and Gina Clowes

After the death of a U.K. teenager, whosecase involved getting two injections of epinephrine in the same thigh, therewas some suggestion that a second dose should have been given in the oppositethigh.

Thesuggestion was that this might increase the circulation of epinephrine in thebody. However, Dr. Brown does not seea concern with injecting a second dose in the same thigh. As this is such a largemuscle, she says you are highly unlikely to inject in the exact same location.

However, she agrees that there is no problem with injecting a second dose in the opposite thigh (to the first dose) if there is no barrier to doing so.

Ina severe anaphylactic reaction, Dr. Brown says there is a lot of fluid leakage fromthe blood vessels internally, which makes it hard for your body to pump enoughblood through your heart. Its often helpful for a person to lie down with feetelevated when suffering from a serious reaction.

Youare helping them to circulate their blood the best if theyre lying down,she says. And after youve given epinephrine, youre helping to circulatethat epinephrine the best if theyre lying down.

Shediscussed U.K. research into cases of patients who had died from anaphylaticshock. Some patients worsened after they stood up quickly or were propped up duringtheir extreme reactions. The lack of blood flow to the heart may have led to aheart attack, which contributed to the fatal outcome.

Dr.Brown recommends that patients experiencing active anaphylactic symptoms shouldlie down, if possible. However, I certainly see lots of kids who aresitting comfortably for hours in our emergency department, and they dont allneed to be lying down. She says this recommendation is probably mostimportant when a patient feels faint or light-headed or early in a reactionthat is progressing rapidly.

Importantly, she says, not everybody is going to be best off lying down. Dr. Brown gives the example of someone whos having respiratory distress as a symptom. If its upper airway difficulty, with what we call stridor the kind of noise where youre having trouble breathing in that person often needs to be sitting up and leaning forward. This is a position that allows your airways to be the most open.

In addition, she says that individuals who are vomiting should be lying on their side to reduce the chances of choking.

This is an issue of concern particularly in schools. The teacher should never send a kid in school on their own to the nurses office, says Dr. Brown. You dont know how the disease is going to progress between the classroom and the nurses office.

She recommends sending someone with the student, at a minimum, so they can monitor and advocate for the child or teen if needed. If the child is feeling faint, then help should be brought to the child, rather than sending the child to get help.

According to Dr. Brown, studies have shown there is epinephrine in your system for at least 6 hours. Its at a higher level for about an hour, and it peaks around 5 minutes. Theres a pretty decent amount [circulating] for 40 minutes.

Shesays people often think epinephrine only lasts 15 minutes because thats whenyoure suggested to take a second dose if needed. But it doesnt mean that thereisnt medication still on-board from the first dose.

Evidenceshows most people only need one dose of epinephrine, says Dr. Brown. One reasonis that it lasts for the duration of most reactions. A second reason is thatepinephrine stabilitizes mast cells, making them less twitchy, aneffect that may last even after the epinephrine is gone.

She says a third factor is that, even for patients who dont get epinephrine, a lot of these reactions will burn out on their own. Thank goodness for that, because everybody [with food allergies] has a first reaction where they arent carrying epinephrine! she says. Of course, you never want to count on it burning out on its own, so you should always treat anaphylaxis early with epinephrine.

Thegood news is: There are a number of studies that have looked at what happenedto epinephrine when you freeze it. Theyve shown that both refrigerating andfreezing epinephrine does not degrade epinephrine. So it maintains high levelsof epinephrine.

Dr. Brown and colleagues have further investigated what happens to auto-injector devices when frozen. Dr. Brown was senior author of a study [by Alex Cooper et al] in which 104 EpiPens were frozen for 24 hours, then thawed while their mates [from EpiPen 2-Pak cartons] were left at room temperature. The frozen-then-thawed devices fired a similar amount of epinephrine to their never-frozen paired device. When another 104 frozen-thawed devices were opened unfired, there was no damage to the syringes or other device parts.

This research didnt find any evidence of adverse effects to the device of having been frozen for 24 hours. It looks like freezing has pretty minimal effects on EpiPens, said Dr. Brown. She cautions that this research looked only at EpiPens, not other auto-injectors, and the impact on other devices could be different.

Dr. Brown explains that heat is much more problematic than cold. Previous research has shown that you can definitely see the degradation of epinephrine itself with high heat. She says temperatures in a car on a hot, sunny day can exceed 194 degrees F, and a device exposed to this sort of heat could have degradation of the epinephrine.

The device itself can also be negatively impacted by heat. Her teams ongoing research [lead investigator Samuel Agosti] is examining the impact of high heat, and exposing EpiPens and EpiPen Jrs to 183 degrees F for 8 hours. In this study, Dr. Brown reports, were seeing differences in the amount of epinephrine fired from heated-then-cooled devices compared with their unheated pairs [from EpiPen 2-Paks]. We are also having trouble getting some devices out of the cases.

Sherecommends replacing a device that has had significant heat exposure. Shecautions if it feels hot to the touch, I would say thats pretty suspect that thedevice is not reliable anymore. Theres a risk there.

Dr. Brown doesnt think so. She says that in the United States, we have safe devices that have really maximized needle lengths for serving a wide range of population and different-sized people. Longer needles might be more suitable for some extremely large patients, but those longer needles might be long enough to reach bone in many normal-weight patients.

She notes that the goal is to get the medicine into the thigh muscle, and the device mechanism that pushes the drug out also plays a role. So needle length isnt the only factor. Although there will always be challenges to meet every patients needs, Dr. Brown believes the options available the devices in the U.S. are probably doing a reasonable job, all things considered. She notes there is even a third dose option now, the Auvi-Q device for infants.

Dr. Brown had no concerns about airport scanners. Shes not aware of any specific research in this area, but doubts an airport scanner would have any ability to impact your dose of epinephrine or the functioning of the device.

Her team [led by investigator Andrew McCray] has researched this easy mistake to make and the news is not good for an EpiPen that has gone through the laundry. While prescribing information does not address what to do if the device is submerged in water, the EpiPen website says the carrier tube is not waterproof and that a submerged device should be replaced. However, Dr. Brown said: I still thought that they would do pretty well because it looks like a robust device that was based on a design developed for the military. But our results are not encouraging.

She reports that water gets lodged in the outer layer of the device, and more importantly the amount of drug that fires appears to be impacted. She recommends following the advice to replace an auto-injector that has gone through the washing machine.

Epinephrinedevices do continue to maintain a high level of the labeled dose of epinephrineas they age. While Dr. Brown recommends keeping current, unexpired deviceswhenever possible, she has little concern about the four-month expiration dateextension that the FDA issued on certain lot numbers during periods of shortage.

However, as Dr. Brown explains, the amount of epinephrine is only part of the story. There are epinephrine metabolites that occur as the medication ages. The safety or toxicity of these metabolites in the body in expired medication is unknown. While the theoretical risk of these metabolites shouldnt prevent use of a potentially life-saving medication in an emergency, it is a good reason to keep a current device on hand.

Shes aware that many allergy families keep older auto-injectors in case of emergency, but cautions that the level of epinephrine is getting pretty low after two years, and the level of metabolites is probably getting fairly high. Two years is probably a reasonable limit for keeping back-up devices. After that, its really time to just toss them in your med recycling bin.

With heat, light exposure or over time after expiration, epinephrine is degraded and metabolites begin to increase. Epinephrine metabolites can exceed FDA recommended levels well before the medication shows any discoloration, says Dr. Brown. However, some pharmacists still perpetuate the notion that as long as the medication is clear, its OK to use.

If the epinephrine has been exposed to heat, it can have a fairly significant increase in epinephrine metabolites and not be discolored. You cant rely on color tell you whether or not your device is safe to use, she cautions.

If it is discolored, it is unsafe. But if it was exposed to heat and is clear, it could still have significant degradation.

Although Dr. Brown acknowledges the concern of Benadryl masking anaphylaxis, she says that is giving antihistamines way more power than they have in allergic reaction. Her view is that if a reaction is going to be an anaphylactic one, an antihistamine wont stop it. There is no argument that epinephrine is the drug of choice to treat anaphylaxis, a life-threatening allergic reaction. But for a mild symptom, such as a mild runny nose or slight rash, she says its fine to give an antihistamine. Youre not going to mask anything. As long as youre still keeping a watchful eye for symptom progression.

She shares two caveats, though. Dr. Brown is among a growing number of experts who prefer a non-sedating antihistamine, such as Zyrtec, rather than Benadryl, as the latter is more sedating. She recommends this to avoid confusion between drowsiness from the medication and drowsiness related to anaphylaxis.

The second caveat is that if an antihistamine has been given for a single symptom, such as hives, you would still count that symptom as one system affected, even if the symptom resolves. She explains that if youve treated hives with an antihistamine and theyve improved, but half an hour later you go on to start vomiting, now youve hit two systems. According to most care plans, you would meet criteria for using epinephrine.

Interestingly, research shows conflicting benefits of corticosteroid medication in anaphylaxis. First, Brown explains there is a misconception that steroids take a long time to work, but theres some evidence that steroids actually can work within 30 minutes.

However, research from Canada suggests that steroids given prior to admission into the hospital increased intensive care admissions. She notes that its unclear if that truly was an effect of the steroids, or if perhaps steroids were being used instead of epinephrine.

There is also a notion that steroids decrease the risk of a biphasic or secondary reaction. But a review of cohort studies suggests that steroids are not having an impact on biphasic reactions. Brown concludes that theres really not a lot of great evidence to support that steroids are doing anything in anaphylaxis.

There are many other drugs and supports that can help a patient recover from an anaphylactic reaction such as fluids, oxygen, antihistamines, albuterol and other asthma medications. The additional drugs and monitoring available are why it is so important to seek medical care during an anaphylactic reaction.

Thefirst thing to remember is that [patient emergency anaphylaxis] care plans havea very low threshold for giving epinephrine. Often you are giving epinephrinebecause you meet this two-system criteria for giving epinephrine, Dr. Brownexplained.

Thatthreshold for using epinephrine by a lay person, who is not in a medicalsetting, is lower than it would be in a hospital. In the emergency departmentBrown notes:

The physician has the advantage of having you on monitors, of knowing your vital signs, what your exam is like, what kind of a timeframe were talking about. Time is very important in anaphylaxis, and thats not something that is incorporated into emergency care plans. The doctors will incorporate all that information into the decision-making about whether or not its appropriate to give more epinephrine at that time, whether or not they want to do something else, or whether they just want to watch further.

All of those may be safe and appropriate options in the emergency department setting, while you might make very different decisions if youre in the community and following your care plan.

Dr. Brown cautions that its important to understand that there is no rhyme or reason to food allergy reactions and that any reaction can become the bad reaction. You can have had very mild reactions all of your life, and then your next one can be really severe.

At the same time, it is wise to be aware that if youve had very life-threatening reactions in the past, then that may increase your chance of having one again, she says.

While our individual histories are things we cant necessarily change or impact, co-factors are things that we can be aware of. Dr. Brown explains that co-factors are things like exercise, heat, alcohol consumption, illness and menstruation. All of those can exacerbate your allergic reaction.

So if youre having a mild allergic reaction and you go out for a jog, that may really flare up that reaction. Or if youre having a bit of a reaction and you go take a hot shower, that may really activate all your masts cells and you may come out of the shower just covered in hives. Some people are exacerbated by cold, so they might go out on a very cold day and find that that sets them off. Illness certainly decreases peoples threshold for reaction. So they may find that they can tolerate a food pretty well most of the time, and then when they are ill have a decreased threshold for reacting to that food. Some women find around their menstruation theyre much more likely to react to certain foods, she says.

Dont be afraid of epinephrine. It is unfortunately so hard for so many people to get past the mental idea of giving themselves [or a child] a shot, but it invariably makes you feel so much better when youre having an allergic reaction, says Dr. Brown. It only does good things, it only keeps you safe. It really is a wonder drug in anaphylaxis.

She puts it succinctly: Dont be afraid to use it yourself. Dont be afraid to use it for your child. Youre only going to make things better.

Allergic Living and Gina Clowes extend our appreciation to Dr. Julie Brown for her generous time in helping to create this go-to resource for the food allergy community. Dr. Brown is an emergency medicine physician and co-director of emergency medical research at Seattle Childrens Hospital, with study interests in epinephrine, auto-injectors and anaphylaxis. Gina is the founder of AllergyMoms.com.

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All About Epinephrine: What It Does in a Reaction, How Long It Lasts, When It Gets Hot or Cold - Allergic Living

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