Epinephrine auto-injectors are the mainstay of emergency treatment for anaphylactic allergic reactions, but despite many years of widespread use, important questions about them remain unanswered. At the American Academy of Allergy, Asthma, and Immunology (AAAAI) annual meeting that was supposed to have occurred last weekend — cancelled, like many others, as a precaution to prevent COVID-19 spread — a number of research presentations on these products were scheduled. Here are some of the highlights.

Don’t Look to Restaurants to Have EpiPens on Hand

If your child experiences a food allergy anaphylaxis event at a restaurant, the chances that epinephrine would be used to mitigate the attack may not be good, according to Abstract #010.

The Cross-Canada Anaphylaxis Registry counted 695 cases of emergency department anaphylaxis cases since 2011, finding that although 144 cases occurred in restaurants, epinephrine at the restaurant was used in 38.5% of the cases — and was used in just 48% of cases in which a patient was known to have a food allergy, reported Jordan Trevisonno, MD, of Royal Victoria Hospital/McGill University Health Centre in Montreal.

“Outpatient epinephrine use was low among participants who suffered anaphylaxis in a restaurant,” he said. “There is a need for educational programs promoting epinephrine use and allergen avoidance for restaurant staff and patrons. Policies encouraging restaurants to learn how to use and to stock epinephrine auto-injectors are required.”

Trevisonno and colleagues said that most of the cases — 114 of the 144 cases — involved children, and that most commonly, the anaphylaxis cases — 18.4 % — were triggered by peanut allergies.

“Studies suggest that food allergy and anaphylaxis are increasing and that fatality may occur outside the home,” the researchers said. “No large-scale prospective studies have assessed the management of anaphylaxis in restaurants. Our goal was to evaluate clinical characteristics and management of anaphylaxis occurring in restaurants.”

The registry includes cases in five provinces of Canada, and the case met the definition of anaphylaxis as defined by the position paper of the European Academy of Allergy and Clinical Immunology on the management of anaphylaxis in childhood.

Most Episodes Occur at Home

Another abstract (#009) by McGill researchers prepared for the meeting found that most anaphylaxis events occurred in the household where the allergic individual lived.

Medical student Sabrina Bartolucci, MSc, reported that from 2011 to 2019, there were 2,092 cases of anaphylaxis presented to the emergency department at Montreal Children’s Hospital. Of those cases in children, 1,652 (78.97%) of the total occurred in the home, she reported.

In this study, the most frequent trigger of an anaphylaxis event was a food allergy, which occurred in 1,469 cases or 88.98% of the cases, and the most frequent food trigger was peanuts — 19.61% of the events, she reported.

“Patients more likely to receive epinephrine prior to arrival were those with previously identified food allergy,” the researchers said. “The frequency of food-induced anaphylaxis is increasing, the majority of reactions occurring at home. Our findings demonstrate that most episodes of anaphylaxis in children occur at home and are triggered by food. Those with previously identified food allergy, who are older, or have anaphylaxis triggered by certain foods, are more likely to be treated with epinephrine prior to arrival in the emergency department. Future efforts should focus on identifying barriers to the use of epinephrine in younger children.”

Expired EpiPens Still Work

Auto-injector epinephrine pens, often carried by individuals with known food allergies, still are effective even after their “expiration” dates, researchers reported.

In Abstract #007, Brittany Boswell, MD, of Seattle Children’s Hospital/University of Washington, reported that even after 24 months past the expiration date, 84% of the 77 EpiPens tested retained at least 90% of epinephrine concentration.

Boswell and colleagues performed a literature search to find studies of expired auto-injectors, and located eight relevant articles that scrutinized the content of pens that had exceeded their purported shelf life by 4 months, 12 months, or 24 months.

“Epinephrine auto-injectors provide life-saving treatment in the event of anaphylaxis,” she reported. “Common challenges include short expiration dates, high replacement costs, and epinephrine auto-injector shortages. Studies suggest that epinephrine auto-injectors might provide therapeutic levels of epinephrine after their expiration dates, and during a shortage, one manufacturer recently extended expiration dates of certain epinephrine auto-injector lots by 4 months.”

In the literature search, the team located studies that considered eight auto-injectors that had been expired for 4 months — all of them still contained more than 90% epinephrine concentrations — a level demanded by the FDA for effectiveness. Of 28 auto-injectors that had expired 12 months earlier, 75% still contained more than a 90% concentration of epinephrine. And 84% of the devices that had expired 24 months previously also contained at least 90% epinephrine concentrations.

“Expired epinephrine auto-injectors may contain more than 90% epinephrine concentration, which would assist with the costs and challenges of maintaining in-date supplies, particularly in times of epinephrine auto-injector shortages,” Boswell said. “However, given the uncertainty of optimal epinephrine dosing, epinephrine pharmacokinetics in anaphylaxis, and effects of epinephrine degradation products, more information is needed.”

If You Wash it, Dump it

Another group of researchers at Seattle Children’s Hospital determined that if you accidentally wash an EpiPen or dump it under water, it may not work properly and should be discarded (Abstract #016).

The group, headed by Julie Brown, MD, of the University of Washington, tested 68 pairs of same-dose, same-lot, post-consumer expired EpiPens.

Fifteen of the pens contained 0.3 mg of epinephrine and 53 of the pens contained 0.15 mg of epinephrine. One of the pairs was washed in its carrier tube through the colors cycle of a top-loading washing machine, while its pair was kept at usual conditions. Both were then fired into meat. The increase in meat mass and decrease in device mass were measured to estimate the mass of solution fired.

The researchers found that washed devices fired a greater mass of epinephrine solution into the meat and devices lost more mass during firing versus controls (P<0.0001). Ten washed devices failed to deploy the needle cover after firing. The effect of washing did not differ by dose or expiration date, and 15 dissected devices had dry needles and plungers.

“Washing EpiPens impaired their function,” Brown and co-authors reported. “These devices should not be used if accidentally placed through a washing machine cycle.”

Asked for her perspective, Punita Ponda, MD, of Northwell Health in Great Neck, New York, said: “Treatment of anaphylaxis is of paramount importance but the shortages of epinephrine autoinjector availability make this very difficult.”

“In addition to the need for improvement of knowledge of appropriate use and appropriate storage, we need to work on making the epinephrine devices more easily available to our patients,” she told MedPage Today. “This is an important access to healthcare need with an increasing number of the population being diagnosed with food allergy or other conditions that require the presence of an injectable epinephrine device.”

“Expired epinephrine auto-injectors are likely to be okay well beyond their expiration date if stored appropriately as the medication is likely stable for long periods of time unless they are in, say, a very hot environment such as the glove compartment of a hot car,” Ponda continued. “However, when washed, it is possible that the device mechanism malfunctions. The medication inside may still be fine, but the auto-injector is unable to deliver an appropriate dose to the patient, possibly due to dysfunction of the structure of the device.”

Not Only Kids

The number of elderly patients being seen in emergency departments because of anaphylaxis events is increasing, researchers from Stanford University reported in Abstract #014.

Led by Anna Arroyo, MD, the team mined data from the Nationwide Emergency Department Sample from 2006 to 2015, relying on hospital codes to identify acute allergic reactions to medications, venom, food, or other triggers of the anaphylaxis events.

Overall, 1,709,696 emergency department visits for acute allergic reactions and 44,937 emergency department visits for anaphylaxis occurred among elderly U.S. residents during that time frame, Arroyo and colleagues reported. Just focusing on anaphylaxis events, the team found that the number of visits increased from 2,906 visits to 5,298 — a significant trend (P<0.001). The proportion of emergency department visits for anaphylaxis also increased over time, from 14 to 26 per 100,000 emergency department visits among the elderly (P<0.001).

However, hospitalizations for anaphylaxis decreased despite the increase in visits, Arroyo said. At the beginning of the study the hospitalization rate was 57%, but that had decreased to 47% by the end of the study period.

“The risks of anaphylaxis in the elderly are often unrecognized because often their comorbid conditions make the presentation of the episode not as clear-cut as for younger patients, who often present with more ‘classical’ symptoms of hives, and shortness of breath after, say, eating a new food,” Ponda noted. “For the elderly, symptoms can often be more subtle or different such as chest pain, generalized redness of skin, and altered mental status.”

Refresher Course Needed in ED

In Abstract #006, a survey of emergency department personnel found that 61% of the time doctors rarely take the time to make sure parents and children know how to correctly operate epinephrine auto-injectors.

More troubling, just 7% of the emergency department personnel who responded to the survey correctly advised parents how to use the auto-injectors, reported Miriam Samstein, MD, of Zucker School of Medicine/Hofstra University in Hempstead, New York.

Samstein said that most of the emergency room personnel who filled out the survey didn’t answer correctly that when using the auto-injectors the device was recommended to be held against the thigh for 3 seconds.

Respondents who did not counsel parents relied on ancillary providers or outpatient pharmacists, but 12% had a dedicated emergency department pharmacist to review discharge medications. The respondents suggested that barriers to proper counseling included lack of time, lack of training devices, lack of physician knowledge, and confusion due to numerous auto-injectors on the market.

“Although it has been several years since changes have been made to EpiPen labels this information has not been fully incorporated into clinical practice in emergency departments,” Samstein said. “Alternative care models, including dedicated emergency department pharmacists, could help alleviate the burden on physicians. In addition, dedicated training for emergency department personnel on epinephrine delivery devices would be helpful.”

Last Updated March 16, 2020