New Study: More Than One in Ten Reactions Treated With Epinephrine Requires More Than One Dose

In a recent study investigating how food allergy patients, parentscaregivers carry and use epinephrine auto-injectors, only 44 percent of survey respondents reported that they always carry at least one auto-injector. Far fewer respondents – 24 percent – followed the recommended practice of always carrying two auto-injectors or more. Now a new study funded by FARE and published in the Annals of Allergy, Asthma & Immunology finds that among epinephrine-treated reactions, more than one in ten required multiple doses of epinephrine to relieve dangerous reaction symptoms.

During regular office visits to a New York City food allergy clinic between 2009 and 2011, a randomly distributed questionnaire was used to assess the histories of pediatric food allergy patients. The young patients (ages 0 to 17; median age 2.5) were predominantly male (59 percent), Caucasian (77 percent) and privately insured (96 percent). Follow up data, including reports of subsequent reactions, were collected six months after the initial questionnaire. The follow up did not identify any fatalities among study participants.

Of the 684 questionnaires completed, about one-quarter (166 patients) reported reactions requiring epinephrine, for a total of 221 epinephrine-treated reactions. Factors that increased the risk of a reaction requiring epinephrine included history of using allergy medication, history of albuterol use or asthma, allergic rhinitis (hay fever), and allergy to specific foods including shellfish, seeds, milk, wheat, tree nuts and egg.

To identify risk factors associated with reactions requiring multiple epinephrine doses, researchers compared the 197 reactions that responded to one auto-injector with the 24 reactions that were treated with two auto-injectors or more. The factor most strongly associated with reactions treated with multiple doses of epinephrine was the need for oxygen treatment. Reactions treated with oxygen had five-fold greater odds of also requiring multiple auto-injectors. However, a history of atopic conditions like asthma and hay fever did not increase the odds of a reaction requiring two or more doses of epinephrine rather than just one dose.

Notably, allergy to milk was associated with three-fold greater odds of a reaction requiring two or more doses of epinephrine. No other specific food allergy was linked to a statistically significant increase in reactions treated with multiple epinephrine doses. This may have been influenced by the ages of the children and their likelihood of exposure to milk compared to other allergens; early introduction of potentially allergenic foods was not recommended at the time of the study, and dairy products are widespread and difficult to avoid. Regardless, this finding highlights the importance of educating food allergy families and the broader public that milk allergy is increasingly common, is less frequently outgrown than in the past, is not equivalent to lactose intolerance, and can result in reactions that are life-threatening and sometimes fatal.

About half of the reactions requiring epinephrine were treated with an auto-injector within ten minutes of the onset of symptoms, while one reaction in five was treated after a delay of 30 minutes or more. For more than half of the treated reactions, the first or only auto-injector was administered by a patient, parent or caregiver, rather than a medical professional.

There was no association between a delayed first epinephrine dose and the requirement for one or more additional doses. However, two or more auto-injectors were more frequently used in reactions first treated by emergency medical services (EMS) personnel than in reactions first treated by patients, parents or caregivers. This suggests that for some severe reactions requiring multiple doses of epinephrine, an auto-injector was either not available or not used prior to the arrival of emergency services. Given recent reports that only one food allergy patient in four always carries two doses of epinephrine, physicians and food allergy educators should emphasize the importance of carrying two auto-injectors at all times.

Learn more about anaphylaxis on FARE’s website. You can also learn how to be prepared to manage anaphylaxis confidently by taking FARE’s free 15-minute online course, How to Save a Life: Recognizing and Responding to Anaphylaxis.