Epinephrine in Anaphylaxis: Too Little, Too Late

Jay Adam Lieberman; Julie Wang


Curr Opin Allergy Clin Immunol. 2020;20(5):452-458. 

In This Article

Moving the Immovable Object

Defining the problem and understanding the causes, as undertaken above, will hopefully allow for some improvement in epinephrine usage. To date, studies examining trends in epinephrine use are inconsistent, with some showing increase use of epinephrine and others showing no change over years, but as stated earlier, rates are still lower than desired.[28,29,32,44,45]

Thus, measures should still be taken to improve this.

Improving Knowledge of Anaphylaxis Management and the Role of Epinephrine

Common sense would suggest that increasing knowledge of anaphylaxis would increase epinephrine use; however, there are essentially no data to show that this is true.

Identification of anaphylaxis is the first step in the process, and efforts have gone into improving knowledge surrounding this area, yet gaps remain amongst providers and patients/caregivers alike. The current working, clinical definition of anaphylaxis proposed in the United States was meant to identify clinical cases where epinephrine is warranted.[46] Indeed, these criteria have been shown to be highly sensitive, but not very specific.[47] As introduction of these criteria there has been only a small change in delivery of care.[28,29] In fact, one single-center study did show improved usage of epinephrine by the desired intramuscular route (versus subcutaneous) in their ED after publication of these guidelines; however, no changes to overall epinephrine use was seen.[45]

Specific forms of education on anaphylaxis hold promise as well. Simulation studies, for example, can show immediate postsimulation knowledge gained via testing strategies but unfortunately there are no outcomes studies to show that this can change clinical practice.[48,49] Education sessions or videos can also increase knowledge and confidence of treatment for both providers and caregivers,[50,51] but this is only assessed by pretest and posttest scores and not by any clinically meaningful outcomes.

Anaphylaxis action plans are designed to guide the patient/caregiver in recognition and anaphylaxis, thus streamlining the decision-making process for them.[52] Unfortunately, the effectiveness of these action plans has never been tested.

Thus, as clinicians, we need better ways to assess whether simple education can make a difference in outcomes and if so, what type of education is most effective and how often re-education would be needed.

Increasing Availability of Epinephrine

As discussed earlier, not all areas of the world have access to epinephrine autoinjectors, and whenever available, epinephrine is not always filled, carried or used. Cost is a major factor in extending availability, and this issue is not easily fixed.[53] One attempt to address this concern is to allow 'stock' epinephrine in public places, such as schools, airplanes, and other community locations. Currently, there are little data to show how effective this can be, though some data generated from modeling studies demonstrate potential cost-effectiveness but little real-world data to show the utility of this approach.[54–57]

Increasing Carriage of Autoinjectors

Increasing carriage of the device when available is difficult. Investigators have attempted methods, such as text reminders and even financial incentives; however, these appear to have little overall effect or may not be feasible on a large scale.[58,59] One study noted that the type of auto-injector device may influence carriage, suggesting that convenience may play a role in carriage.[60] Thus, at this point, clinicians are left without much data to suggest any specific means that have been proven to increase carriage rates.

Increasing Routes of Delivery of Epinephrine

Currently, epinephrine is recommended to be used by the intramuscular route with intravenous infusion for more severe, intractable cases. There are other routes of administration being studied currently, such as intranasal and sublingual epinephrine.[61,62] These routes hold promise, as there is an assumption that removing the barrier of a needle, will hopefully increase the likelihood that epinephrine will be used by patients (although this has not been proven). Currently, data on the intranasal form has only been published as an abstract.[62] Questions remain whether regulatory agencies will approve these medications based on bioequivalence data to the intramuscular form, as it is very unlikely they will be able to be studied against either placebo or intramuscular form in the clinical setting (i.e. a placebo-controlled or head-to-head study in anaphylaxis).