Retire the advice to send patients to the emergency department after epinephrine use for observation

Food allergy action plans state that if epinephrine is administered to “immediately call 911 and seek care in the nearest medical facility.”¹ Such guidance has been based on expert opinion given the risk of persistent (eg, refractory) or biphasic reactions after initial epinephrine use. In addition, practitioners, health care organizations, and policy groups are cognizant of potential litigation if patients have adverse outcomes associated with anaphylaxis management, despite following treatment protocols. Patients with food allergy are educated that anaphylaxis is a medical emergency and have been strongly encouraged that if they (or their child) receive epinephrine, they should be transported to an emergency department (ED) in case they require additional resuscitative care and to be monitored for symptom recurrence.² However, existing data, although limited, do not support a one-size-fits-all approach necessitating ED care for asymptomatic patients after they have been treated with epinephrine.³

Food allergy fatalities are exceptionally rare, occurring in fewer than 0.69 cases per million-person years (less than 1/500,000 persons with known food allergy).⁴ Biphasic food allergic reactions occur in approximately 3.92% of cases, with only 7.7% of cases requiring a second dose of epinephrine (and a third dose in fewer than 2.2% of cases).^4,5 Food as an anaphylaxis trigger is associated with a decreased odds of a biphasic reaction (odds ratio, 0.62; confidence interval, 0.4–0.94).⁶ Furthermore, there is no evidence (nor has ever been any evidence) that routine ED care for asymptomatic patients who have received prehospital epinephrine improves outcomes or that ED observation to monitor for biphasic reactions is necessary or reduces fatality risk.

Utilization of emergency medical services (EMS) in this setting may also be detrimental to the health care system. From 2008 to 2016, there were more than 400,000 US ED visits for anaphylaxis, with visit numbers doubling among all patient ages and tripling in children. These visits are associated with long observation periods, ED overcrowding, and potential for missed work and school.⁷ A 2018 cost-effectiveness study used Markov modeling to simulate the health benefits and costs associated with activating EMS and ED observation after epinephrine use for peanut allergy, compared with a “wait and see” approach where the child was observed at home.⁷ In a 20-year horizon, for the emergency pathway, the incremental cost per life year saved was $142,943,447 and cost per death prevented was $1,349,335,651, assuming an estimated 10-fold decreased risk of anaphylaxis fatality with observation. The emergency observation pathway was cost effective only at a 500-fold fatality risk reduction and a 75% probability of additional care escalation on arrival—both fairly implausible assumptions.⁸ Thus, although the theory of recommending post-epinephrine ED observation is understandable, this policy is not supported by data for a nonsevere allergic reaction that promptly resolves with appropriate treatment at home, and it should be reserved strictly for patients requiring a second epinephrine dose or for reactions that do not respond to initial dosing. To our knowledge, no study has revealed an increase in fatality in Europe where an “always transport to the ED” policy does not exist, and we are not aware of any data or anecdotal reports of increases in fatality during coronavirus disease 2019 (COVID-19) in the United States, when the “wait and see” strategy was implemented.

Beyond a high cost and lack of clear benefit, there is an opportunity cost to the health care system for a pathway that forces observation of resolved allergic reactions. This was apparent during the early COVID-19 pandemic, when hospitals, EDs, and emergency service capacity were overwhelmed caring for dying and critically ill patients with COVID-19, although still having to manage “normal emergencies.” In this context, in the spring of 2020, Food Allergy Research & Education (FARE) recognized post-epinephrine patients with treated and resolved allergic reactions were, compared with other diagnoses at the time, a lower priority in terms of needing ED care. FARE temporarily changed their food allergy action plan to adapt the wait-and-see approach so long as the patient had access to a second epinephrine dose and had access to someone comfortable monitoring for symptom recurrence.⁹ This change may have limited unnecessary ED utilization for food allergic reactions for otherwise stable children who could be safely managed at home; however, data supporting this impact have not been made available for analysis yet. Furthermore, the revised recommendation may have had the positive impact of promoting epinephrine use for patients and families who previously were hesitant to administer epinephrine autoinjectors to avoid going to the ED.¹⁰ Unfortunately, FARE guidelines have reverted back to recommending that for all patients with food allergy receiving epinephrine, EMS be called and the patient taken to the ED, universally.¹

This brings us to the fall of 2022, when pediatric hospitals and EDs became inundated with a simultaneous surge of patients with respiratory infections from respiratory syncytial virus, influenza, and the COVID-19 omicron variant. This surge has overwhelmed already strained ED and inpatient units in many areas, an effect that is compounded by significant staffing challenges. To alleviate these burdens, food allergy action plan advice specific to epinephrine use should once again adapt, and we should revert to a “watchful waiting” policy regarding when to seek emergency care after epinephrine use for asymptomatic patients when allergic reactions promptly resolve with treatment.^3,8,9

Moreover, it is our opinion that the “watchful waiting” advice needs to be a new standard to food allergy care policy patients with resolved allergic reactions at home (eg, after a single dose of epinephrine). Immediate activation of EMS and ED transport has minimal demonstrated benefit in this population. This advice, although well intentioned, is not (nor has ever been) supported by data.³ Such policy is long past the time of retirement, especially in an age where autoinjectors in the United States are exclusively distributed as a twin pack (meaning that most patients should have a second dose at home), most patients are administered multiple twin packs, and the standard of care is to train patients and caregivers how (and when) to use an epinephrine device according to an action plan. However, it must be noted that such advice may not be uniform, parents may express confusion and uncertainty in execution as for what symptoms “necessitate” administering epinephrine, and to consider whether the practice has on-call access to a trained nurse or allergy clinician to help walk a parent through such scenarios. Where and when available, pathways that incorporate emergency telehealth visits in such circumstances could be used or developed for additional support. As such, it is paramount to identify patients at risk for adverse outcomes (eg, low health literacy) who may benefit from ED care to ensure safe outcomes. This sentiment we express herein is shared by others in the field, in a recent publication.³

Anaphylaxis can constitute a medical emergency, but this is a unique situation in that patients with a known risk are equipped with a rapid-acting home medication that quickly resolves the emergency in 93% of cases. Clinicians diagnosing food allergy and prescribing epinephrine must educate patients and caregivers to differentiate between nonsevere reactions that likely do not require EMS activation and ED care from severe reactions, giving them options on how to proceed, rather than dictating a default response where all such patients are instructed to seek emergency care, a response that has never been justified by data that such actions improve outcomes. This may mean that allergists stop relying on action plans from advocacy groups that are not in line with current evidence and create their own action plans or at the very least modify existing ones, with revised language to better contextualize when activation of EMS is more indicated vs when it is not (eg, for anaphylaxis not responding to epinephrine, rather than automatically for a child treated with epinephrine who has no signs of a reaction progressing).

Biphasic reactions are rare for most pediatric patients experiencing a food allergic reaction, in particular ones rapidly treated with epinephrine. When epinephrine is used, additional epinephrine doses are infrequently required. Universal ED transport and observation for resolved allergic reactions after home epinephrine use may be a comforting option for many but could also lead to misunderstanding of epinephrine risk and create a financial barrier to appropriate home management. Reflex activation of EMS for patients with resolved allergic reactions lacks data to support that it is necessary, and evidence of consistent benefit in such policy is absent. Thus, it is an unnecessary practice to routinely send such patients to the ED solely because epinephrine was used, unless symptoms do not promptly resolve or the reaction recurs. There are many examples where such unnecessary resource utilization diverts attention and resources from true medical emergencies. It is paramount that we not wait until the next health care crisis before we act to prevent unnecessary health care utilization for food-induced reactions that can be safely managed in the community and optimize stewardship of valuable health care resources.