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Prescribing epinephrine for anaphylaxis self-treatment

Prescribing epinephrine for anaphylaxis self-treatment
Literature review current through: Jan 2024.
This topic last updated: Nov 30, 2022.

INTRODUCTION — Epinephrine is the drug of choice in the treatment of anaphylaxis and is available in many parts of the world in the form of epinephrine autoinjectors for self-treatment [1,2]. However, when prescribing these devices, clinicians must teach patients how and when to use them and dispel fears about adverse effects. Autoinjectors may be lifesaving for patients but only if patients are willing and able to use these devices effectively. All of the current devices used for self-administration of epinephrine are designed for intramuscular injection. Studies are underway regarding alternative routes not requiring injection such as intranasal, sublingual, and inhaled [3].

PHARMACOLOGY — Epinephrine is a sympathomimetic agent with multiple actions that can reverse the symptoms of anaphylaxis. (See "Anaphylaxis: Emergency treatment".)

Beneficial effects — Epinephrine acts as an agonist at alpha-1 receptors to mediate increased vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema. Agonist effects at beta-2 receptors result in bronchodilation and decreased mediator release from mast cells and basophils (table 1) [4].

Adverse effects — Even when injected properly, epinephrine is often associated with minor and transient adverse effects such as tremor, dizziness, palpitations, anxiety, restlessness, and headache (table 1) [4].

In contrast, serious adverse effects such as myocardial ischemia are rare after injection of a 0.3 mg dose in an adult or a 0.15 mg dose in a child. Such effects occur more commonly with epinephrine overdose, especially after intravenous administration. Reluctance to administer epinephrine due to fear of adverse cardiac effects should be countered by the awareness that myocardial ischemia and dysrhythmias can also occur in children and adults with anaphylaxis who have not received epinephrine treatment and in whom no cardiovascular disease can be found after the episode [5,6].

Unintentional injections and other injuries — The rate of unintentional injections of epinephrine from autoinjectors is high [7,8], with more than 15,000 such events being reported voluntarily to the American Association of Poison Control Centers from 1994 to 2007 [8]. A systematic review of 69 unintentional injections found that 91 percent involved a finger or thumb [7]. In another large retrospective series of 365 unintentional injections specifically to the hand, all patients had complete resolution of symptoms without the need for admission or surgery [9]. In this series, warm water soaks alone were used in 32 percent, and no drug therapy was administered in 77 percent. In 23 percent, various vasodilatory therapies were given (including topical nitroglycerin paste or local injection[s] of phentolamine). Most patients had resolution of symptoms within two hours.

Other injuries related to use of epinephrine autoinjectors include lacerations, embedded needles, and injection site infections (Clostridium perfringens) [10].

Contraindications — There are no absolute contraindications to the administration of epinephrine for anaphylaxis [1,2]. Therefore, all patients who have experienced anaphylaxis should have access to epinephrine for self-treatment, including pregnant patients at risk and patients who may be at greater risk for serious adverse effects, such as older individuals with cardiovascular disease.

AVAILABLE DEVICES

Autoinjectors — The following preloaded epinephrine autoinjectors are available in the United States:

EpiPen (brand name) – Containing 0.3 mg per dose

EpiPen Jr (brand name) – Containing 0.15 mg per dose

Authorized generics of EpiPen – Containing 0.3 or 0.15 mg per dose

Authorized generics of Adrenaclick – Containing 0.3 or 0.15 mg per dose (brand name no longer available)

Auvi-Q (brand name; Allerject [brand name] in Canada) – Containing 0.3 mg, 0.15 mg, or 0.1 mg per dose (provides audible directions to guide user)

In Canada (and Europe among others) another device, the Emerade autoinjector, is available as 0.15 mg, 0.3 mg, and 0.5 mg.

Availability and cost — Depending on the country, other brands of autoinjectors, generic autoinjectors, and prefilled, sealed syringes containing epinephrine are available. It is important that prefilled syringes be sealed, since epinephrine in unsealed syringes degrades rapidly [11]. Cost may also be an issue in some health systems. A study using a commercial insurance database in the United States found that with the advent of generic devices, most patients paid $20, although about 1 in 13 paid over $200 [12].

Differences in the design and use of epinephrine self-injection products available need to be considered in the context of patient skills and preferences [13].

Prefilled syringes — A prefilled syringe (Symjepi [brand name]) containing 0.15 mg or 0.3 mg of epinephrine per dose was approved by the US Food and Drug Administration and should offer a more affordable alternative to autoinjectors. The 0.15 mg dose is labeled for patients 15 to 30 kg (33 to 66 lbs), and the 0.3 mg dose is labeled for patients ≥30 kg (66 lbs). The medication is contained in a light-blocking plastic case, and patients must remove the needle cap, insert the needle into the anterolateral thigh, and depress the plunger to dispense the dose.

The prescription of ampules of epinephrine and a syringe as a low-cost alternative has been discussed, but this approach suffers from potential dosing errors when used by laypersons in an emergency [14]. The provision of a syringe prefilled with epinephrine, stored away from light and kept for a brief period such as three months, has also been considered as a low-cost alternative but suffers from concerns about sterility and stability [15]. These options may be more suited to resource-poor regions.

Training — We suggest designating the specific name and description of the product intended to be dispensed on the prescription order and providing patient education that is specific to that product. Training devices that do not contain needles or epinephrine are available to clinicians and patients from the manufacturers in most cases and are sometimes dispensed at the pharmacy when the patient fills the prescription. In addition, manufacturers provide detailed instructions and videos online. Studies suggest that recurrent training may be required [16].

Number of doses to dispense — There are no global consensus guidelines about how many autoinjectors should be dispensed for each patient [2]. Decision-making might include past reaction history, risk of severe anaphylaxis, access to additional care, and other factors. Many allergy specialists prescribe at least two for all patients, and some prescribe more. The following should be considered:

A systematic review and meta-analysis that included 86 studies found that 7.7 percent of anaphylaxis cases from any cause were treated with more than 1 dose of epinephrine. Considering epinephrine-treated reactions where the subsequent doses were administered by heath care professionals, the rate was 11 percent for food allergy and 17 percent for venom allergy [17].

There is a theoretical concern that overweight or obese teenagers and adults may be underdosed (on a per kg basis) when treated with the 0.3 mg autoinjector, although this has not been proven [4,18].

The distance between the patient's home/work/school and the nearest medical facility also impacts the number of doses that should be available to the patient. The World Health Organization (WHO) and Anaphylaxis Canada recommend the availability of one dose for every 10 to 20 minutes of travel time to a medical emergency facility [19].

Concerns about overprescribing additional units and generating excessive cost have been raised [20]. As an example, having multiple units available at school for each at-risk child when many units are already available in the school for other children may not be necessary [21].

DOSING — In North America, several brands of epinephrine autoinjectors are available in doses of 0.15 mg and 0.3 mg. One brand (Auvi-Q) also has a dose of 0.1 mg available, which is labeled for use in infants and toddlers 7.5 to 15 kg (16.5 to 33 lbs) [22]. The 0.15 mg dose is labelled for those weighing 15 to 30 kg (33 to 66 lbs). The 0.3 mg dose is labelled for adults and children weighing ≥30 kg (66 lbs). Large or obese individuals should have access to multiple doses. Dosing in small children is discussed below. (See 'Small children' below.)

Adults — Autoinjectors with 0.3 mg of epinephrine per dose are appropriate for adults.

Large or obese adults — Very large or obese adults should have access to at least two doses of epinephrine.

In patients with significant adipose tissue on the anterolateral thigh, the needle of an epinephrine autoinjector may not be of sufficient length to reach the underlying muscle, and compression of the tissue during injection is minimal. Compared with subcutaneous injection, intramuscular injection of epinephrine results in higher and more rapid plasma concentrations and is therefore the recommended route of delivery [23]. However, in a series of 28 patients, needle length was not sufficient to reach the underlying muscle of the anterolateral thigh in 68 percent of patients [24]. The issue was more common in females, even those with normal body mass index (BMI). These findings may raise concerns about suboptimal delivery, although human treatment studies have not been undertaken to quantify the potential differences in serum dose and kinetics. In addition, a retrospective chart review of emergency department patients with anaphylaxis, mostly children, found that the need for a second dose did not correlate with overweight status, suggesting repeat dosing is not a result of obesity or suboptimal medication delivery [18]. Having a second autoinjector available addresses the concern that treatment may be inadequate for this or other reasons, pending further study of the implications of needle length and patient weight.

Children — In most countries, epinephrine autoinjectors are available in only two fixed doses: 0.15 mg and 0.3 mg. One manufacturer has developed a 0.1 mg dose (Auvi-Q [brand name]). The availability of specific doses in autoinjectable form presents difficulties in delivering an appropriate dose to many children. The recommended dose of epinephrine for children is 0.01 mg/kg, up to 0.3 mg. Therefore, the premeasured autoinjectors technically contain the recommended dose only for a 10 kg (22 lbs), 15 kg (33 lbs) or a 30 kg (66 lbs) individual.

Small children — The prescribing information for autoinjectors containing 0.15 mg of epinephrine indicates that the dose is intended for patients weighing 15 to 30 kg (33 to 66 lbs). Using these manufacturers' guidelines, children weighing 25 kg (55 lbs) would receive the 0.15 mg dose, although the optimal dose for a child of that weight is higher (0.25 mg). Furthermore, little information is provided about dosing in a child weighing less than 15 kg (33 lbs), other than the caveat that dosing decisions are the responsibility of the prescribing clinician.

Examples of dosing issues raised by fixed-dose autoinjectors in infants and small children include the following:

For a 7.5 kg (16.5 lbs) child – The 0.1 mg autoinjector delivers 133 percent of the ideal dose, and the 0.15 mg autoinjector delivers 200 percent of the ideal dose.

For a 10 kg (22 lbs) child – The 0.15 mg autoinjector delivers 150 percent of the ideal dose.

For a 12.5 kg (27.5 lbs) child – The 0.1 mg dose delivers only 80 percent of the ideal dose, while the 0.15 mg autoinjector delivers 120 percent of the ideal dose.

For a 20 kg (44 lbs) child – The 0.15 mg autoinjector delivers only 75 percent of the ideal dose, while the 0.3 mg autoinjector delivers 150 percent of the ideal dose.

For a 25 kg (55 lbs) child – The 0.15 mg autoinjector delivers only 60 percent of the ideal dose, while the 0.3 mg autoinjector delivers 120 percent of the ideal dose.

Despite the lack of precision in dosing with autoinjectors, the alternative (ie, drawing up epinephrine in a syringe to obtain the correct weight-based dose) is associated with delayed administration, inaccurate dosing, and potential loss of the dose. A study of the ability of parents without medical training to utilize an ampule and syringe after receiving verbal and written instructions in a nonurgent setting found this method to be error-prone and slow [14].

One study indicated that children generally tolerate higher doses of epinephrine without serious adverse events. In a randomized trial, children (aged four to eight years and weighing 15 to 30 kg [33 to 66 lbs]) who were at risk for anaphylaxis received either 0.15 mg or 0.3 mg of epinephrine intramuscularly [25]. The higher dose resulted in significantly higher systolic blood pressures compared with the lower dose but was also associated with transient nausea, palpitations, and headache.

Suggested approach — To provide additional guidance to the clinician, a clinical report from the American Academy of Pediatrics reviewed the risks and benefits of selecting the 0.15 mg or the 0.3 mg fixed doses for children of different weights [26]. The report references European guidelines, suggesting the 0.15 mg autoinjector may be used for infants weighing as little as 7.5 kg (16.5 lbs) [27]. Subsequent to this report, the 0.1 mg Auvi-Q (brand name) became available in some countries and is labeled for use in infants and toddlers 7.5 to 15 kg (16.5 to 33 lbs). The following summarizes our suggested approach based on these guidelines, but specific decisions should be individualized according to patient characteristics and caretaker preferences (eg, severity of allergy, comorbid conditions, cost/availability of autoinjectors, caretaker proficiency with using a syringe and ampule) (table 2 and table 3):

Ideal dosing for infants under 7.5 kg (16.5 lbs) would require an ampule and syringe or a prefilled syringe. The 0.1 mg autoinjector (only available as Auvi-Q [brand name]) could also be considered for infants near the upper end of this weight range if an autoinjector is believed to have important benefits over other delivery devices.

For infants/children weighing 7.5 to 10 kg (16.5 to 22 lbs), the clinician has the following prescribing option:

Prescribe a 0.1 mg (ideal) or a 0.15 mg autoinjector (option if the 0.1 mg autoinjector is not accessible).

For infants/children weighing 10 kg (22 lbs) up to 15 kg (33 lbs), either the 0.1 mg (matches manufacturer labeling but only one product available) or 0.15 mg autoinjector is appropriate. However, as noted above, use of the 0.1 mg dose becomes less ideal as the child approaches 15 kg.

When the 0.1 mg autoinjector is an option, the American Academy of Pediatrics suggests using this device from 7.5 kg (16.6 lbs) to less than 13 kg (28.6 lbs) [28].

Children weighing 15 kg (33 lbs) to less than 25 kg (55 lbs) can receive the 0.15 mg dose.

Children weighing 25 kg or more (55 lbs or more) can receive the 0.3 mg dose autoinjector.

Dosing might be individualized for children with severe past reactions, to select the higher of the two fixed doses at lower weights.

In Canada where the 0.5 mg Emerade device is available, the manufacturer suggests using this for adults >60 kg, and a Canadian position statement suggested this be prescribed for those weighing 45 kg (99 lbs) or more [29].

KEY TEACHING POINTS — There are several important teaching points that should be emphasized when instructing patients in optimal use of epinephrine autoinjectors. These should be reviewed with patients at regular intervals. Patient information that reiterates these teaching points is also available. (See 'Information for patients' below.)

Anaphylaxis is unpredictable — Patients should understand that anaphylaxis is highly unpredictable [30]. One exposure to an allergen may result in mild symptoms, while the next causes a life-threatening reaction or vice versa, for reasons that are not fully understood.

Epinephrine is the best treatment available — The patient should be assured that epinephrine is the most effective treatment available for anaphylaxis and that having an autoinjector will enable the patient to start treatment without delay. Fatal anaphylaxis is associated with lack of availability of epinephrine or failure to inject epinephrine promptly [31,32]. This fact may be expressed to the patient as the following: "In most cases of anaphylaxis that prove fatal, the person who died either did not have epinephrine available or had it available but did not use it. Thus, by having an epinephrine autoinjector and knowing how to use it, the patient already has a significant advantage."

Carry the autoinjector at all times — Epinephrine autoinjectors must be carried at all times in order to be available when the drug is actually needed. Patients may make the mistake of having their autoinjectors on hand only in the setting where they spend most time (ie, home, school, or work). However, they may be at particular risk for anaphylaxis when out of their normal routines (eg, during exercise, while dining out, attending celebrations and banquets, or traveling). Thus, patients should devise a way for an autoinjector to be available at all times. This may mean storing autoinjectors in multiple locations or carrying a small bag containing the autoinjector and other essential items that is taken everywhere, without exception.

Antihistamines or asthma inhalers are not sufficient treatment for anaphylaxis — Patients must understand that antihistamines and inhaled beta-agonists can treat some symptoms of allergic reactions (urticaria, pruritus, and bronchospasm, respectively), but they cannot reverse laryngeal edema or hypotension and are too slow-acting to be effective in rapidly developing anaphylaxis (table 1) [1,2].

Antihistamines and asthma inhalers alone may appear to adequately control symptoms in anaphylaxis in some instances, but it is unclear if improvement is due to the medications or the patient's own corrective physiologic responses. Therefore, clinicians and patients must regard epinephrine as the first and best treatment for anaphylaxis.

When to use it — Clinicians should use plain language to explain to patients when to self-administer epinephrine. In the setting of an allergic reaction, patients should use the epinephrine autoinjector immediately if they:

Are having trouble breathing

Feel tightness in the throat

Feel lightheaded or think they might pass out

If treating a child with an allergic reaction, also use the autoinjector if the child:

Is not responding as expected or has altered consciousness during an allergic reaction

Has food allergies and is vomiting repeatedly shortly after eating, especially if accompanied by flushing or hives

Is coughing repeatedly during an allergic reaction (indicating bronchospasm)

Had previous anaphylaxis and develops widespread hives after a suspected or known ingestion of the allergen

Has definitely eaten a trigger food that previously caused severe anaphylaxis and is having any symptoms [33,34]

How to use it — Epinephrine should ideally be injected into the mid-outer part of the thigh, into the underlying muscle. Intramuscular injection is preferable to subcutaneous injection, as it results in more rapid systemic absorption [23,30]. Patients should be instructed to hold the device with a closed fist (ie, like a baton, with thumb/fingers away from either end) as accidental injection of the thumb/fingers or palm can occur if the autoinjector is inverted [7]. Children may not hold still for an injection, and caregivers should hold the child's leg firmly in place. The autoinjector should be held in place for at least three seconds after the injection. Instructions for different devices suggest 3 to 10 seconds, although most of the medicine is released from the device within the first second [35].

Patients should be instructed to stay with other people if possible during an allergic reaction. There is no need to undress before using the autoinjector, as the needles are designed to penetrate clothing. However, we typically instruct patients to raise skirts or lower pants, if possible, to avoid an obstruction such as a buckle or contents of a pocket.

The clinician should demonstrate how to use the specific autoinjector that is being prescribed, by using the specific training device for that autoinjector. Detailed written instructions are provided separately (see 'Information for patients' below). Manufacturers also provide DVDs and videos on their websites.

Use it without delay — Patients should understand that epinephrine is most effective when given within the first few minutes of an allergic reaction.

Call for help and go to the emergency department — If the patient is alone, epinephrine should be self-administered first and then the patient should call for help and be transported to the nearest emergency department (ED) as soon as possible in case the symptoms of anaphylaxis worsen or recur without further exposure to the trigger. It is important to make clear to patients that the reason for proceeding to the emergency department is the possibility of worsening or recurrent symptoms. Some patients misinterpret instructions to go to the emergency department as evidence that epinephrine is dangerous and that they must be examined whenever they have self-administered it. This, in turn, can cause them to avoid use of the autoinjector.

During the early part of the coronavirus disease 2019 (COVID-19) pandemic, with infectious risks increased for ED visits, the necessity of transport to the ED for all episodes of allergic reactions treated with epinephrine was questioned [36]. Indeed, most reactions respond to one dose of epinephrine and do not require additional treatment. However, a decision not to proceed to an ED could also carry serious risks should the symptoms worsen and require additional interventions. Provider advice regarding home management should be individualized, and we favor having the patient proceed to an ED. It may be reasonable to have home management under circumstances such as close proximity to an ED, confidence in patient self-assessments, prompt and excellent response to treatment, access to additional autoinjectors and comfort with use, and patient circumstances (such as past reactions being mild/self-limited, not having significant asthma, etc). Circumstances that would argue against home management include any reluctance to treat, lack of autoinjectors, patient not being comfortable, past serious reactions, etc. These considerations are not an exhaustive list and ultimately such decisions would need to be made in communication with a health care provider.

Even if the emergency department is in close proximity or emergency medical services are en route, the epinephrine autoinjector should still be administered.

If patients become lightheaded, they should lie down with their legs elevated, if possible, in order to increase blood flow to vital organs. Similarly, if the patient loses consciousness in the caregiver's presence, the patient should be placed on their back with legs elevated.

Patients should never be propped up during anaphylaxis. Rising to an upright position during severe anaphylaxis has been associated with sudden death due to the "empty ventricle syndrome" [37]. Patients should be transported to an emergency medical facility in the supine position.

More than one dose may be needed — Patients should be advised that a second dose may be needed if symptoms do not appear to be stabilizing or improving, and this may be given 5 to 15 minutes after the first dose [30].

Practice with the training device — Autoinjectors are dispensed with a training device that is identical to the autoinjector but does not contain a needle or medication. Patients/caregivers should practice periodically with a training device. They should also use the trainer to teach others who may need to administer the epinephrine if the patient is incapacitated. They should also be warned that the actual/live device may have more recoil than the trainer and they should be prepared for this and continue to hold the device firmly against the thigh [38].

Teach others — Patients should be encouraged to inform and educate appropriate friends, caretakers, colleagues, and food providers about their allergic condition. It may be essential that those around them are able to recognize an allergic reaction and react effectively, both by administering epinephrine and calling for assistance if the patient is incapacitated.

Patients and caregivers should use the training devices to teach others how to administer epinephrine. (See "Food allergy in schools and camps".)

Replace the autoinjectors prior to expiration — Epinephrine autoinjectors have a limited shelf life and should be replaced prior to expiration. Some patients renew their prescription on their birthday or at the start of the calendar year in order to link renewal to an annual event.

Autoinjectors have a window to inspect for discoloration of the solution or precipitated material in the solution, which are signs that the solution is losing potency. However, ideally, expired autoinjectors should also be replaced, even if the solution remains clear.

Use of expired autoinjectors — Patients should be informed that it is preferable to use an out-of-date autoinjector rather than not injecting epinephrine at all [39]. At least three studies have found that expired autoinjectors retain significant potency, even up to four years after the expiration date:

One study found that epinephrine solutions that were within 24 months of their expiration dates still contained at least 90 percent of the labeled dose [40].

Another study found that among 31 expired autoinjectors, those less than 12 months past expiration contained 88 to 100 percent of the intended dose, and the oldest (50 months past expiration) contained 84 to 88 percent of the intended dose [41].

Another study that measured the active enantiomer found that 65 percent of devices retained >90 percent of activity over almost two years [42]. The 0.3 mg devices maintained potency better than the 0.15 mg devices: within 36 months post expiration, 93 percent of adult devices and 66 percent of pediatric devices retained >90 percent potency.

Storage — Patients should be instructed to keep epinephrine autoinjectors or prefilled syringes in locations with neutral temperatures (waist pack, purse, cabinets) rather than locations where the unit may overheat or freeze (glove compartment of a car, in an uninsulated bag on the beach). The devices should not be refrigerated.

Freezing and thawing appears to be better tolerated than storage at excessively hot temperatures [43-45]. A study examined the effects of storage of nine EpiPens for 12 hours in various locations inside a car on a summer day and found that temperatures within the car reached as high as 62°C (143°F; highest in the glove compartment) and that this single exposure resulted in decrements of 3 to 14 percent in the concentration of epinephrine, without changes in the appearance of the solution [46].

Based on limited data and information from the US Food and Drug Administration, autoinjectors are unlikely to be adversely affected by radiograph equipment at airport security [47,48].

AREAS OF UNCERTAINTY FOR THE PRESCRIBING CLINICIAN — There are several areas of uncertainty for prescribing epinephrine and teaching patients about when it is appropriate to inject the medication. These situations require clinical judgment.

Who is at risk for anaphylaxis? — Epinephrine is indicated for persons who have experienced anaphylaxis to an agent they may encounter again, and for patients with idiopathic anaphylaxis. However, there may be less obvious circumstances where prescribing epinephrine is also appropriate [2,49,50]:

It may be unclear from the clinical history whether anaphylaxis occurred and clinical judgment may be needed to decide whether it did occur.

An individual may have experienced a mild reaction to an allergen that is known to cause severe reactions (eg, a peanut/tree nut allergy). As an example, it would be reasonable to prescribe epinephrine for a child with severe eczema who was found to have peanut allergy and placed on a peanut-free diet but who had displayed only flares of eczema after eating peanut and never had a more serious reaction. Such patients may be at risk for anaphylaxis if subsequently exposed to the culprit allergen [51].

An individual may have had an allergic reaction with clinical features that may indicate a higher risk of anaphylaxis on a future exposure, such as reactions to trace amounts of a food.

There may be comorbid diseases or medications that increase the risk for a severe reaction, such as asthma or the use of beta-blockers.

Oral allergy syndrome — The risk of a systemic reaction in a patient with oral allergy syndrome and the relative indications for prescription of self-injectable epinephrine are reviewed separately. (See "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Indications for epinephrine'.)

Instructing patients when to inject epinephrine — Certain symptom combinations, particularly with known or likely exposure to an allergen, are indications to inject epinephrine, as reviewed above [34]. However, there are circumstances where it may be appropriate to instruct patients to self-inject when such symptoms have not occurred or are mild:

If symptoms are mild but the patient is in a remote location.

If the symptoms are mild but the reaction appears to be progressing rapidly.

If the patient or caregiver is uncertain about the severity of the reaction, in which case it is preferable to administer epinephrine rather than withhold it.

If there has been a known ingestion of a food or an insect sting that previously caused a severe reaction, and any symptoms develop.

Knowledge about the nature of the exposure is also helpful in deciding whether to inject epinephrine.

For example, if it is known that a food allergen was rubbed into the eye but definitely not ingested, then progression to anaphylaxis is unlikely and symptoms such as eyelid angioedema would not be a reason to inject epinephrine. However, if the allergen was definitely ingested, the victim had a history of severe anaphylaxis to the same trigger, and eyelid angioedema was noted, it would be reasonable to inject epinephrine.

A child with asthma and an upper respiratory infection who ate a presumably safe meal and then exercised and developed severe wheezing is not likely experiencing anaphylaxis but rather an asthma exacerbation and would warrant inhaled bronchodilator therapy. In contrast, a child with severe asthma and peanut allergy who ate a peanut cookie and developed severe wheezing would warrant injection with epinephrine.

Responsibilities of older children and adolescents — As children at risk for anaphylaxis mature, they need to become responsible for recognizing and treating anaphylaxis. In an online survey of 88 pediatric allergists, participants were asked about the age at which children are able to begin assuming these responsibilities [52]. These allergists most frequently responded that children aged 9 to 11 years should be able to describe some symptoms of anaphylaxis, recognize the need for epinephrine, and demonstrate correct use of an autoinjector. By age 12 to 14 years, most allergists expected children to take some responsibility for self-administering epinephrine when needed. They individualized the timing based on assessment of patient readiness factors, including medical history, developmental level, and ability to demonstrate correct autoinjector technique. It is important to note that a similar survey of parents and caregivers indicated that these individuals perceived the transition period as roughly three years earlier than the allergists, indicating the need to discuss whether children are capable of taking on these responsibilities on an individual basis [53].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anaphylaxis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

Basics topic (see "Patient education: How to use an epinephrine autoinjector (The Basics)")

Beyond the Basics topic (see "Patient education: Using an epinephrine autoinjector (Beyond the Basics)")

For patients with diagnosed anaphylaxis, three key steps include prescription of epinephrine, patient education, and follow-up evaluation [30]. Epinephrine should always be prescribed in the context of a comprehensive care plan, including instructions on allergen avoidance, as well as indications for injection of epinephrine and instructions on activating additional emergency services (eg, calling 911).

Printable action plans — Printable action plans are available from multiple sources:

The American Academy of Allergy, Asthma, and Immunology has devised an "Anaphylaxis Emergency Action Plan" (available in English and Spanish) that can be personalized and provided to any patient who has experienced anaphylaxis. This plan provides clear instructions for patients about how to treat an anaphylaxis episode and gives both the clinician and the patient an opportunity to personalize the instructions.

Action plans specific to children are also available (form 1).

Versions of action plans designed specifically for patients with food allergy are available from the Food Allergy Research and Education (FARE) website.

SUMMARY AND RECOMMENDATIONS

Duties of clinician – When prescribing epinephrine autoinjectors for anaphylaxis self-treatment, clinicians must also provide patient-specific advice about when and how to administer epinephrine and dispel fears about its adverse effects. (See 'Introduction' above.)

Pharmacology of epinephrine – Epinephrine is a sympathomimetic agent with multiple actions that can reverse the symptoms of anaphylaxis (table 1). (See 'Pharmacology' above.)

SafetyEpinephrine will cause transient and minor adverse effects in most patients, even when used properly. However, patients should be reassured that serious adverse effects, such as myocardial ischemia, are rare with the doses delivered by an autoinjector. Furthermore, untreated anaphylaxis itself is associated with myocardial ischemia and dysrhythmias. Thus, all patients with past anaphylaxis should have access to epinephrine for self-treatment. (See 'Adverse effects' above.)

Available devices – Several different autoinjector devices are available, which vary in ease of use and cost. Prefilled, sealed syringes containing epinephrine are another option that is more commonly used in resource-limited settings. Once a device is selected, we suggest designating the specific name and description of the product on the prescription order and providing patient education that is specific to that product. (See 'Available devices' above.)

Dosing of autoinjectors – Most epinephrine autoinjectors are available in doses of 0.15 mg and 0.3 mg. One manufacturer produces a device for infants that contains 0.1 mg (table 2 and table 3). The manufacturer's labelled dosing ranges differ from some expert opinions reflected here.

The 0.3 mg dose is appropriate for children and adults weighing 25 kg or more (55 lbs or more). Large or obese individuals should have access to multiple doses. (See 'Dosing' above.)

Dosing in young children and infants is more difficult, as the available doses result in doses either below or above the ideal dose for many. The 0.15 mg dose may be used for children between 10 and up to 25 kg (22 to <55 lbs) if the 0.1 mg dose is not available. If the 0.1 mg autoinjector is available, the switch to the 0.15 mg dose could be at 13 kg (28.6 lbs). (See 'Children' above.)

For infants and small children weighing 7.5 kg (16.5 lbs) to <13 kg (<28.6 lbs), the 0.1 mg dose is ideal, but the 0.15 mg dose can be prescribed if the 0.1 mg dose is unavailable. (See 'Small children' above.)

Teaching points – There are several important teaching points that should be emphasized when instructing patients in optimal use of epinephrine autoinjectors, which address most patients' areas of concern and confusion. This information should be reviewed with patients at regular intervals. (See 'Key teaching points' above.)

Issues requiring clinical judgement – Clinical situations arise in which it is not clear if epinephrine should be injected. As an example, it is reasonable to instruct a patient with severe anaphylaxis to food who subsequently had a known ingestion of the culprit food to inject epinephrine even before any symptoms have developed. (See 'Areas of uncertainty for the prescribing clinician' above.)

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Topic 388 Version 32.0

References

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