Who needs to carry an epinephrine autoinjector?
ABSTRACT
Patients who have had anaphylaxis or who are at risk of it (eg, due to food allergy or Hymenoptera hypersensitivity) should carry an epinephrine autoinjector at all times. However, the risks and benefits must be considered on an individual basis, especially in patients with atherosclerotic heart disease, elderly patients on polypharmacy, patients receiving allergen immunotherapy, those with large local reactions to insect stings, and individuals with oral allergy syndrome.
KEY POINTS
- Based on current data, there is no absolute contraindication to epinephrine for anaphylaxis. And failure to give epinephrine promptly has resulted in deaths.
- Clinicians concerned about adverse effects of epinephrine may be reluctant to give it during anaphylaxis.
- Education about anaphylaxis and its prompt treatment with epinephrine is critical for patients and their caregivers.
INJECTOR OPTIONS
Epinephrine autoinjectors come preloaded for prompt delivery of the drug. They are intended primarily for use by patients themselves in unsupervised settings in suspected anaphylaxis. Simplicity of use and safety must be considered in such a setting so that patients can use the device correctly and are not incorrectly dosed.
Several models are commercially available, with different ergonomic designs and sizes. EpiPen, the first one marketed in the United States, was introduced in 1987. One device (Auvi-Q) contains an audio chip that gives step-by-step instructions at the time of use. It is hoped that this device will reduce errors in usage during this stressful time for patients and caregivers.
In the United States, epinephrine autoinjectors contain either 0.15 or 0.30 mg of the drug, but some clinicians believe this may not be enough. The UK Resuscitation Council recommends 0.50 mg for patients over age 12,37 and an epinephrine autoinjector with that dose is available in Europe.
Subcutaneous vs intramuscular delivery
The package insert for some epinephrine autoinjectors says the injector can be used to treat anaphylaxis by both subcutaneous and intramuscular administration. However, the routes are not equivalent.
The goal in anaphylaxis is to quickly achieve high tissue and plasma epinephrine concentrations, and studies have found that injection into the vastus lateralis muscle, but not the deltoid muscle, results in faster time to peak plasma concentration: 8 minutes for injection in the vastus lateralis muscle and 34 minutes for subcutaneous delivery.10,11 In addition, injection in the vastus lateralis muscle results in a higher peak plasma concentration than the subcutaneous or deltoid route. Based on these data, intramuscular injection into the vastus lateralis muscle in the thigh appears to be the preferred route of administration of epinephrine.
Obese patients may need a longer needle
Research on the original autoinjector was conducted by the US military, which wanted a rapidly effective and easy-to-use antidote for battlefield exposure to poison gas. The resulting device had 2 separate spring-loaded syringes, 1 containing pralidoxime chloride and the other atropine sulfate. To enable its use through the thick fabric of a chemical warfare suit, the needles were 2.2 cm long.
The first commercial autoinjector to contain epinephrine was made by Survival Technology (Bethesda, MD) in the mid-1970s. The manufacturer considered a 2.2-cm needle to be too long, and the first commercially available epinephrine autoinjector, EpiPen, had a 1.43-cm needle for adult use.
Since then, needle lengths have ranged from 1.17 to 2.5 cm to accommodate different skin-to-muscle depths, with shorter needles for children and longer needles for obese adults.38
However, the prevalence of obesity is high and continues to rise.39 Obesity raises concern that the needles in epinephrine autoinjectors may be too short for the preferred intramuscular delivery, resulting in subcutaneous deposition.
A study that used computed tomography of the thigh found that 1 (2%) of 50 men and 21 (42%) of 50 women studied had a subcutaneous tissue depth greater than 1.43 cm, the needle length in EpiPen. These were not anaphylaxis patients, but the findings suggest that many patients—especially women—may be getting subcutaneous instead of intramuscular delivery with this device.40
Another study that used ultrasonography showed that the 1.43-cm EpiPen needle was too short for 36 (31%) of 116 adults.41 Women were 6.4 times more likely than men to encounter this problem. Other risk factors include higher body mass index, short height, and thicker thighs.
Emerade, an injector with a 2.5-cm needle, is available in some European countries. A longer needle may be helpful in some cases. but we do not yet have enough data to determine the optimal needle length.
Conversely, some children may need shorter needles and may in fact be at risk of having the needle penetrate bone.42 The US Food and Drug Administration recently approved a shorter needle for an epinephrine autoinjector (Auvi-Q) to be used in children weighing 7.5 kg to 15 kg.
BARRIERS TO USING EPINEPHRINE AUTOINJECTORS
Many patients do not use their epinephrine autoinjector in times of anaphylaxis or do not have one with them. Common reasons cited by respondents in a survey43 of 1,385 patients included the following:
They took an oral antihistamine instead (38%).
They never received a prescription for an epinephrine autoinjector (28%).
They thought their symptoms were mild and would resolve with time (13%).
They were afraid (6%). There are reports of accidental injection, typically into fingers, hands, and thumbs. Fortunately, most accidental injections do not require a hand surgeon evaluation or surgery.44 Conservative therapy and monitoring of the injection site are sufficient in most cases.
They could not afford an epinephrine autoinjector (1%).43 Mylan Pharmaceuticals infamously increased the price of its EpiPen to more than $600 for a package of 2 pens. Generic devices are available in the United States but are still too expensive for some patients and are cumbersome to carry.
However, even expensive epinephrine autoinjectors may be cost-effective. Epidemiologic studies have found that patients who did not use an epinephrine autoinjector incurred a higher burden of cost due to emergency department visits and inpatient hospitalizations.45
As a do-it-yourself option, some resourceful patients are obtaining autoinjectors intended for insulin injection, replacing the needle, and filling the injector with epinephrine, at a cost of about $30. (The manufacturer does not endorse this off-label use of their device—www.owenmumford.com/us/patients/if-you-need-to-inject.) Least costly of all is to prescribe multidose vials of epinephrine and regular syringes and teach patients and their caregivers how to draw up the proper dose and give themselves an injection—in essence going back to what was done before 1987.
It was past its expiration date (2%).43 Failure to refill the prescription is common. A California Kaiser Permanente study46 showed that only 46% of patients refilled their epinephrine autoinjector prescription at least once, and the refill rate decreased over time: 43% at 1 to 2 year follow-up, 35% at 3 to 4 years, and 30% at 5 years or longer. Based on these data, it is imperative to educate patients regarding the importance of replacing the epinephrine autoinjector when the old one expires.
NEED FOR PATIENT EDUCATION
Even though prompt treatment with epinephrine decreases fatalities, it continues to be underused in the community. In addition, it is often prescribed without adequate training in its use and appropriate emphasis on the need to keep the device on hand at all times and to replace it in a timely manner if it is used or has expired. Physicians need to educate patients on how to avoid triggers and how to recognize symptoms of anaphylaxis whenever they prescribe an epinephrine autoinjector.
