Q:

8/20/2013
One question that plagues us as the "Food Allergy Action Plan" season is upon us...what is the official recommendation regarding use of epinephrine in patients with a known food allergy who have ingested the allergenic food but have no symptoms? Many practitioners in our area instruct patients that if there are no symptoms, the patient should receive diphenhydramine and be monitored closely. However, a teenager died in our area recently after eating a peanut, and she initially had no symptoms so was given diphenhydramine and was observed as they had been instructed by their doctors. She then began to vomit 20 minutes later and died of laryngeal edema despite 3 rounds of injectable epinephrine.

Given cases like this, do you recommend use of injectable epinephrine if the food allergen is ingested but there are no symptoms? Thank you for this invaluable service!!

A:

Thank you for your inquiry.

There is no “official recommendation” regarding the issue you present. There is no consensus of opinion in this regard, and different physicians utilize different strategies.

This issue has been dealt with in detail in a previous response to a very similar question submitted to our website. I have copied below that question and response. It goes through the polemics involved in how you might determine your own strategy regarding the issue.

Personally, if the situation occurs in the school, I usually will suggest administration of epinephrine immediately, regardless of whether or not any manifestations are present. However, as you can see from the response copied below, and as mentioned, this is a philosophical decision and varies amongst allergists. It is not one which guidelines have addressed definitively to date.

Thank you again for your inquiry and we hope this response is helpful to you.

When to administer epinephrine to a child having a potential anaphylactic episode in school
Question posted 7/30/2013:
I am a school nurse and it is the time of year when we are organizing our student's food allergy and asthma medication orders for the upcoming year. Most of our students are cared for by a large allergy group in town, whose food allergy action plan requires that epinephrine and diphenhydramine be given if "ingestion of the food allergen is suspected", even if symptoms have not developed yet. I called their office and they confirmed that it was their policy to give epi/antihistamines if accidental ingestion is suspected, even if the child appears well and does not have a history of a severe reaction, because that is always the safest course of action and anaphylaxis could occur suddenly/rapidly at any time. I find that I am uncomfortable with this policy due to the fact that I sometimes see children with subjective, vague, or mild symptoms (for example, stomach upset, cheek flushing, or redness around the mouth) which can be associated with questionable or unwitnessed ingestions, for which epinephrine IM would seem to be overly aggressive as the first step. Do you feel that epinephrine and antihistamines for all food allergic children with possible ingestions without symptoms falls within the normal standard of care? Thanks you for your assistance and the service that you provide.

Response:
You have asked a question which has prompted many debates over the years. We are not going to be able to settle this debate definitively in my response to you. However, I will give you my opinion and hopefully enlighten you on the issues underlying this debate and sharpen your appreciation for it.

First of all, your question is extremely timely in view of a recent death from anaphylaxis in a 14 year-old girl. I think you would appreciate the stance of the physicians in your community who have given you instructions regarding the administration of epinephrine to a greater extent if you will take the time to go to the link (ABC News) copied below. From that link you will also hear stories of other fatalities due to anaphylaxis related to the inadvertent ingestion of a food to which the individual was sensitive. These cases illustrate a very important point. That is, the mean time to respiratory or cardiovascular arrest after the ingestion of a food to which a patient is allergic is 30 minutes (Pumphrey RS, Clinical and Experimental Allergy 2000; 30(8):1144-1150). Thus there is very little time for one to act after patients express even the mildest symptom of an anaphylactic event.

Nonetheless, we have all seen children (and adults) who experience initial symptoms such as itching of the back of the throat or nausea after eating a food, and who recover spontaneously. In the practice of Allergy, we do food allergen challenges on a regular basis and observe these spontaneous recoveries. Thus we are all prejudiced by these observations. These personal anecdotal observations have resulted in the debate as framed in this quote from the Journal of allergy and Clinical Immunology:

“Although there is little debate about using epinephrine to treat a SCIT SR” (meaning anaphylactic reactions to injection of an allergen), “there is a lack of consensus about when it should be first used.”

This debate has certainly extended to anaphylactic reactions to foods. The issue is not whether epinephrine is the drug of choice. Clearly it is. Other agents such as antihistamines do not act in time to prevent fatalities. Thus if we are going to prevent a fatality, the only tool we have to do so is epinephrine.

The question then becomes an analysis of risk/benefit ratio. That is, what is the risk of giving epinephrine versus the potential benefit. I have copied below quotes dealing with this issue from the Guidelines for the treatment of Anaphylaxis published by the Washington State School District as well as the medical literature.

"Based on available evidence, the benefit of using appropriate doses of intramuscular epinephrine in anaphylaxis far exceeds the risk…. Consensus opinion and anecdotal evidence recommend epinephrine administration sooner rather than later, that is, when the initial signs and symptoms of anaphylaxis occur, regardless of their severity, because fatalities in anaphylaxis usually result from delayed or inadequate administration of epinephrine.”

Furthermore, from the same source it states: "If a student, known to have anaphylaxis, has an exposure or a suspected exposure to an allergen, epinephrine is to be given immediately and the EMS (911) system activated."

This same source, which I think is an excellent review of the issues you posed with your inquiry, recognizes that this puts a difficult decision-making process upon the shoulders of those administering epinephrine to a child in the school system. It states: "There is a natural reluctance to wait to administer epinephrine until symptoms worsen and you are sure the student is experiencing an anaphylactic reaction. There is the same reluctance to call 911. Many fatalities occur because the epinephrine was not administered in a timely manner.”

Thus, the doubts that you are having are actually universal, and I clearly understand them. However, reviewing all of the quotes above (and others copied for you below) and all of our available evidence, it would be my opinion the instructions you have been given are correct, and I have no problem with them whatsoever. It is quite clear that the potential side effects of administration of epinephrine to a child in the appropriate dose by intramuscular injection are not serious, and comparing these side effects to the potential of saving a life in my opinion favors the administration of epinephrine in the situation that you describe.

Having said this, as I mentioned at the beginning of my response, this answer cannot be dogmatic, and it is certainly recognized that there are differences of opinion amongst experts in this regard. So, in the final analysis, since it would be impossible for us to do a study to compare the two strategies (delayed versus immediate administration), one is left with isolated case reports, personal experience, and one’s own philosophy as to how to act in such a situation as you described.

As you can see from my response, I favor the aggressive approach, and feel that this is the safest strategy for you to employ in the setting in which you work.

The quotes and links copied below below further support support this opinion and are added if you would like to read more references related to you inquiry.

Thank you again for your inquiry and we hope this response is helpful to you.

Anaphylaxis is a potentially life-threatening condition, requiring immediate medical attention. Most fatalities occur due to delay and delivery of the needed medication. Although many medications may be used for treating anaphylaxis, epinephrine is the life-saving medication that must be given immediately to avoid death.

“Practicing implementation of the ECP can be the most effective strategy to overcome the tendency to delay and to decrease the likelihood of a student fatality."

“Epinephrine has long been regarded as the treatment of choice for acute anaphylaxis. This is true despite the recognition of its potential hazards. Alternative treatments - such as antihistamines, sublingual isoproterenol, inhaled epinephrine, and corticosteroids without epinephrine - have failed to prevent or relieve severe anaphylactic reactions. It is therefore inappropriate to use them for the first-line treatment or prevention of anaphylaxis.”

“Experts may differ on how they define the clinical threshold by which they define and treat anaphylaxis. However, they have no disagreement whatsoever that appropriate doses of intramuscular epinephrine should be administered rapidly once that threshold is reached. There is no absolute contraindication to epinephrine administration in anaphylaxis, and all subsequent therapeutic interventions depend on the initial response to epinephrine".

In July 2008, the World Allergy Organization published the following statements:
"Anaphylaxis is an acute and potentially lethal multisystem allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The committee strongly believes that epinephrine is currently underused and often dosed suboptimally to treat anaphylaxis, is underprescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate intramuscular doses."

AAAAI Board of Directors, “Position Statement Anaphylaxis in Schools and Other Child-Care Settings,” 2008,

The Journal of Allergy and Clinical Immunology
Volume 125, Issue 3 , Pages 569-574.e7, March 2010
"Although there is little debate about using epinephrine to treat a SCIT SR, there is a lack of consensus about when it should be first used"

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology