How Could it Happen? When Epi-Pens Don’t Save a Life
A Florida teen named Alexi Stafford died of a food allergy on June 28. One question people ask in the aftermath is how that happened in spite of two epinephrine injections. Medical experts agree epinephrine is the front line treatment for anaphylaxis. Yet it is possible to be the best and still be overrated.
EpiPen manufacturer Mylan ran an advertisement called “Max’s Birthday” in 2012 that suggested parents could relax about potential allergen exposures as long as their children had epineprhine injectors nearby. This prompted the states of Oregon and Massachusetts to sue the pharmaceutical firm for deceptive advertising. In a public statement after Mylan settled the case, Oregon Attorney General Ellen Rosenblum said:
“Severe food allergies are a potentially fatal health risk. Epinephrine injections can save lives in emergencies, but Mylan was extremely irresponsible to suggest to parents that EpiPen is a substitute for vigilantly avoiding their children’s allergens. Our resolution of this case ensures that consumers will understand the limitations of EpiPen as well as its approved uses.”
This is medicine, not magic.
It is important to guard against the temptation to jump to conclusions. For instance an NBC affiliate news station in Miami covered the story by interviewing an expert who stresses the importance of carrying epinephrine at all times, which can lead viewers to surmise that Alexi Stafford neglected to have her epinephrine at the time of her allergen exposure. That is not actually known. Other relevant factors were not discussed in the NBC Miami segment.
The recommended storage temperature range for epinephrine is 20 C to 25 C (68 F to 77 F). The medication can withstand brief exposures to temperatures up to 30 C (86 F) but degrades in quality under extreme heat or prolonged exposure to moderate heat, according to a systematic study of medical literature published in 2016 in the journal Annals of Allergy, Asthma & Immunology. The conclusions of this study downgrade previous warnings about epinephrine stability at extreme temperatures. The research findings state:
“Maintaining epinephrine within this required range is challenging, particularly for patients carrying autoinjectors and during storage in emergency vehicles.”
This gets scant coverage in the “Newly Diagnosed Packet,” an informative guide published by the nonprofit organization Food Allergy Research and Education (FARE). The introductory field guide advises readers to make sure epinephrine is “kept at a safe temperature” without advising what temperatures are safe or what devices might be necessary to maintain the recommended temperature.
The FARE website also has a page entitled “Carrying and Storing Epinephrine,” which provides no specific temperature warning below 100 degrees, implicitly given only in the Fahrenheit scale. This translates to 38 C, which is well above the current research finding for maximum safe temperature either for short term temperature exposure or for long term storage.
Epinephrine is sensitive to light and extreme temperatures. Store it away from direct light and at room temperature.
Do not refrigerate epinephrine, and be careful to prevent the device from freezing. Never keep it in a vehicle, where temperatures can climb to triple digits. These conditions can cause the medication to become less effective.
It bears mention that although FARE recommends against refrigeration, the most up-to-date science on the topic concludes that “Refrigeration of epinephrine appears to reduce degradation,” which is beneficial as long as neither the medication nor the delivery device becomes frozen.
The FARE page about epinephrine storage links to the organization’s online store so I looked at the products on offer for carrying epinephrine injectors. First is the Epinephrine Mate Waist Pack, which the site describes as “very popular with teens.” The product description mentions nothing about temperature control so I telephoned FARE to ask whether this product includes features such as a compartment for an ice pack. The staffer confirmed that it does not and directed me to another product, the Frio Epinephrine Cooling Bag.
Frio products work through evaporative cooling. Originally developed to carry insulin, these items work by wetting the carrier and letting evaporation keep the contents cooler than the surrounding environment. This ingenious system has one major drawback: evaporative cooling is more effective in dry climates than in humid climates.
Researching further to check how effective the frio system is in a humid climate, I found a field test conducted in Mississippi. Average humidity levels are similar in Florida and Mississippi. The field test simulated the conditions of a frio insulin storage bag by using an evaporative cooling towel and conducted the experiment during a ten hour wilderness first aid training course during the summer. The frio towel maintained a temperature of 88 Fwhen wet; temperature spiked upward when the item dried. This is equivalent to 31 C, which is hotter than the latest scientific research deems safe for brief exposures.
A reasonable surmise would be that people who carry epinephrine should not rely on evaporative cooling to protect their medication for prolonged outdoor excursions during the warmer months in humid regions such as Florida or Misssippi. A 2009 study of epinephrine stability under temperature stresses found that the medication degraded below effective levels after four months at high humidity and temperatures of 38 C (100 F). This is little more than the human body temperature the medication could be exposed to when stored in an uncooled waist pack. The FARE Epinephrine Mate Waist Pack is colored black, which increases heat absorption from sunlight. Neither of the two portable FARE storage products carries a caution that it might be inappropriate for certain uses or climates. Informal interviews of people with allergies find that some resort to bulky lunchbox coolers to keep their medication safe.
As high temperatures risk degrading epinephrine before its expiration date, EpiPen manufacturer Mylan is experiencing supply chain problems. In May 2018 Allergic Living announced a shortage of EpiPens across the United States. A report from Colorado found that pharmacies continue to ration EpiPens into July, fulfilling only one Epi-Pen in 30 days even for patients who had been prescribed two pens. Overseas supplies reached critical levels; Australian pharmacists and physicians counseled allergy sufferers to use expired injectors if necessary. Some patients are asking physicians to change prescriptions to alternate brands such as Auvi-Q.
In researching this post I also reviewed portrayals of anaphylaxis in popular movies and television. Fictional symptoms progress with astonishing speed. In one film a character clutches his throat four seconds after exposure, then collapses on his back 14 seconds later. The causes of these Hollywood are known immediately and fictional symptoms never remain mild. In fictional portrayals where epinephrine is administered, full recovery occurs in less than a minute and affectedindividuals resume normal activities without professional medical followup.
Although it is possible for an allergic reaction to begin within seconds, a typical time frame in real life is closer to 20 minutes. This varies by individual and delayed reactions are more characteristic of food allergens as opposed to other substances such as bee stings. Delayed reactions to some food allergens may not escalate to anaphylaxis until several hours after exposure. Fictional depictions should never shape expectations about real world medical emergencies, yet I wonder whether the Hollywood treatment of anaphylaxis had something to do with the victim blaming that followed the death of Alexi Stafford: compressed time scales in fictional depictions can make it seem less plausible that the teen could have had any good reason to return home after the allergen exposure. In reality she may have had her injector and deemed it best to seek out the most qualified person before life threatening symptoms developed.
Delayed administration of epinephrine is indeed a problem and improper administration occurs frequently in anaphylaxis management: a study published in 2017 found that fewer than half of patients were receiving epinephrine at an appropriate time before arriving in an emergency department; those findings recommended improved training for patients and caregivers. Yet it would be a faulty generalization to assume either of those problems occurred in this instance. Maybe, like the short-lived Mylan commercial “Max’s Birthday,” people want to believe that risks can disappear. A 2017 study concluded that the survival rate for anaphylaxis is greater than 99%, which makes it tempting to become complacent. Bloomberg News ran a Freedom of Information Act request and found that US federal authorities received 228 separate complaints of mechanical failures in EpiPen injectors in 2017. An epinephrine injector is a tool, not a talisman. The best safeguard for managing food allergies is to avoid allergen exposures.
Although no blog post can substitute for training from a skilled professional, sometimes people who carry epinephrine are unable to self-administer in an emergency. Symptoms of anaphylaxis manifest in a variety of ways and can resemble mild reactions during the early minutes. When in doubt, experts recommend administering the medicine and calling 911. Nationwide Children’s Hospital has produced an informational video on the topic. Please take a moment to view it; you might save a life.
