Epinephrine Use for Anaphylaxis — A Multi-Incident Analysis
Hospitals:
- Consider the use of epinephrine auto-injectors or prepared anaphylaxis kits with appropriate labelling to support correct epinephrine dose and route of administration.
- Provide regular training using mock scenarios so that healthcare providers maintain a high degree of competency in the accurate preparation of an appropriate dose using the correct concentration and safe administration of epinephrine via the appropriate site.
Prescribers and pharmacists:
- For pediatric prescriptions, weigh the child in kilograms at each encounter to ensure that the correct strength of epinephrine auto-injector (adult versus pediatric) is being prescribed.
Community pharmacy staff and managers:
- Review dispensary processes related to return of products to stock and methods of verifying expiry dates.
INTRODUCTION
Anaphylaxis is an acute, life-threatening, systemic allergic reaction associated with various triggers, clinical presentations, and levels of severity.1 Epinephrine is the only life-saving drug used to treat a person experiencing anaphylaxis. Recent epidemiological studies indicate that the prevalence of anaphylaxis is increasing.2,3 The Canadian Institute for Health Information (CIHI) reported that from 2006 to 2015, there was a 64% increase in the number of individuals for whom an epinephrine auto-injector was dispensed, and children were the top consumers.3 Because of the increased use of epinephrine, there is a need to better understand the potential risks and problems associated with use of this high-alert medication.
A multi-incident analysis was conducted to identify factors contributing to errors when epinephrine was used for the treatment of anaphylaxis and to suggest strategies to prevent or minimize potential harm when epinephrine is used for this indication.
METHODOLOGY
Reports of medication incidents related to epinephrine were extracted from voluntary reports* submitted to three ISMP Canada incident reporting databases (Individual Practitioner Reporting, Community Pharmacy Incident Reporting, and Consumer Reporting), and the National System for Incident Reporting† (NSIR) between April 2010 and October 2016.
The following medication names were used as search terms: “epinephrine”, “adrenalin”, “Epipen”, “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and “Ana-kit”. Almost 200 incidents were identified in the ISMP Canada databases, and 44 were found in the NSIR database. Incidents not related to epinephrine use in anaphylaxis were excluded, which left 146 incidents in the final analysis. The analysis was conducted according to the methodology for multi-incident analysis outlined in the Canadian Incident Analysis Framework.4
QUANTITATIVE FINDINGS
The majority of the incidents were reported to the ISMP Canada databases. Of these reports, wrong dose errors (e.g., Epipen Jr. given to a child weighing 30 kg or greater) comprised the most commonly reported incident type, followed by products being prepared for the wrong patient and wrong quantity dispensed. Over 80% of incidents were caught before the error reached the patient.
Of the incidents reported to ISMP Canada databases, 3.5% of cases resulted in harm to the patient. The most common type of harm incident resulted from the intravenous administration of epinephrine – either due to selection of the incorrect route when ordering epinephrine treatment, or wrong-route administration (i.e., IM route ordered, but administered IV). All of the wrong-route incidents resulted in harm to the patients.
QUALITATIVE FINDINGS
Analysis revealed 3 main themes, each with multiple associated subthemes (see Figure 1). This bulletin describes each of the main themes and selected subthemes, along with illustrative examples.
FIGURE 1. Main themes from the qualitative analysis
THEME: KNOWLEDGE GAPS
Subtheme: Wrong route
For anaphylaxis, epinephrine should be administered intramuscularly (IM); the intravenous (IV) route of administration should be reserved for patients who have not responded to IM doses and those experiencing severe physiologic compromise.5 Wrong-route administration of epinephrine has been previously reported in an ISMP Canada Safety Bulletin6 and elsewhere in the literature.7,8 In a review of more than 600 cases reported to the Pennsylvania Patient Safety Reporting System, wrong-route errors involving IV administration were responsible for 25.4% of all epinephrine adverse events and 63.3% of the harmful events.8 Several studies have attributed this error to a lack of adequate education of healthcare professionals.9
Incident Example
A consumer reported receiving epinephrine by the IV route, rather than the recommended IM route, as treatment for a mild allergic reaction while in the emergency room. She experienced convulsions, angina, tachycardia, a severe headache, and difficulty breathing. As a result, intervention and additional monitoring were required.
Clinical areas and teams that need to treat anaphylaxis should receive regular training, including holding mock scenarios. Although not identified as an issue in this analysis, consider extending this recommendation to medical office staff.5
Subtheme: Wrong dose
Incorrect dose incidents with epinephrine have occurred in both acute care and community settings. One potential contributing factor has been use of the historical ratio expressions (1:1000, 1:10,000) for strength. In 2016, because of an ongoing stream of serious errors related to confusion in understanding ratio expressions, the United States Pharmacopoeia eliminated ratio expressions on single-entity drug products such as epinephrine.10 Therefore, 1:1000 epinephrine products are now labelled as 1 mg/mL, while epinephrine 1:10,000 for IV injection is labelled as 0.1 mg/mL. A second potential factor contributing to incorrect dosing is the need for a dose calculation in the pediatric age group. The epinephrine dose for anaphylaxis in pediatrics must be calculated according to the patient’s weight (0.01 mg/kg, up to a maximum of 0.5 mg);11 this calculation step represents a risk for error.
Incident Example
An infant weighing 6.5 kg was treated with epinephrine in the emergency room for a possible anaphylactic reaction. The calculated dose, based on 0.01 mg/kg, should have been 0.065 mg IM; however, the infant received 0.65 mg IM, 10 times the intended dose. The baby became lethargic, pale, and cyanotic, and experienced cardiac ischemia. The child required an urgent transfer to a specialized pediatric centre and prolonged monitoring. Fortunately, there were no long-term cardiac effects.
Wrong-dose and/or wrong-route errors have occurred when adults with anaphylaxis have been treated with the cardiac resuscitation dose (1 mg IV) rather than the recommended anaphylaxis dose (0.2 to .5 mg IM5 ).6 These errors likely result from the comprehensive life-saving training required by emergency practitioners, who subsequently become more familiar with the cardiac resuscitation than the anaphylaxis treatment dose of epinephrine in adults.
In the current multi-incident analysis, dose-related incidents in the community resulted when prescriptions were renewed for the pediatric auto-injector when, in fact, the child’s current weight would require that the “adult” device be dispensed.
Because each device is designed to supply only a single, measured dose when activated, choosing the correct one is essential.
Practice Tip:
Pediatric patients are at particular risk from confusion and errors related to dose calculation. Verification of the child’s weight before prescribing, dispensing, and administering epinephrine is an important measure to avoid a dosing error.
Pediatric devices contain an epinephrine dose appropriate for a child weighing between 15 to 30 kg (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and is recommended for children (and adults) weighing 30 kg or more.12 In several of the incidents analyzed, verification of the child’s weight at the pharmacy allowed interception and correction of dosing errors before they reached the patient. Current guidelines for pediatric use of epinephrine suggest that “giving a dose that is slightly above the ideal dose appears to be a better option than giving a dose that is below the recommended dose,” given that underdosing may not be effective to treat anaphylaxis.5 So for children who weigh close to 30 kg, practitioners may choose to prescribe the ‘adult’ device, taking into account previous reactions and individual risk factors.
Previous recommendations and actions taken by facilities to support the correct dose and route of epinephrine administration in anaphylaxis are outlined in Box 1.
Subtheme: Insufficient quantity
The subtheme of knowledge gaps regarding the quantity to be prescribed was apparent in reports in which too few devices were prescribed for emergency treatment of anaphylaxis in the community. Current guidelines recommend that each patient be given 2 devices at a time, because up to 30% of anaphylaxis reactions require the administration of more than 1 dose of epinephrine.5 In particular, for children at risk of anaphylaxis, 1 device should be kept at school and 1 device always with the child, either on their person or with a caregiver.
BOX 1. Measures taken to support correct dose and route for epinephrine injection6
Subtheme: Erroneous deployment
Accidental or erroneous deployment of the auto-injector represents the last knowledge gap subtheme. Epinephrine auto-injectors are commonly carried by patients for self-administration should they experience symptoms of anaphylaxis; however, these devices can be difficult to use if patients or caregivers are unfamiliar with them. For example, accidental injection of epinephrine into the thumb of the person administering epinephrine has occurred, likely as a result of a knowledge gap about device deployment. This type of incident reinforces the need for practitioners to regularly confirm patients’ and caregivers’ understanding of the proper and safe use of these devices, both for therapeutic effect and to avoid injuries. Practitioners are encouraged to use a “teach back” method to confirm patient understanding.
THEME: PROCESS PROBLEMS
Several reports described patients receiving an auto-injector device labelled with another person’s name. This situation can result when a prescription prepared for a specific patient is returned to stock in the pharmacy, because the patient either does not pick up the prescription or declines to purchase it because of cost. These types of incidents highlight problems in 2 community pharmacy processes—the process to return a product to stock, and the dispensing process for labelling and verification of both the outer packaging and the device inside the box.
Incident Example
An Epi-Pen was dispensed for a child. The caregiver at school noticed that the device was labelled with someone else’s name, even though the outer box was labelled correctly. The school notified the parents, who contacted the pharmacy. The pharmacy determined that the device provided for the child had previously been returned to stock without removal of the old label.
Practice Tip:
Pharmacy staff is encouraged to review their processes for:
- returning devices to stock;
- verifying labelling of the outer packaging and device; and
- checking expiry dates at the time of dispensing
Other pharmacy processes deemed problematic were dispensing expired epinephrine auto-injectors and failure to enter refills on prescription order entry.
THEME: PRODUCT FLAWS
Three brands of epinephrine auto-injector—EpiPen, Twinject, and Allerject—were available in Canada during the period from which the data set was extracted. The latter 2 brands are no longer marketed. Common look-alike / sound-alike (LASA) incidents were reported when prescribers confused Twinject with Twinrix (hepatitis A and B vaccine). Fortunately, these errors were caught by community pharmacists during patient counselling.
Incident Example
A physician wrote a prescription for “Twinrix” with 6 refills. The pharmacist clarified with both the patient and the physician that the desired medication was Twinject.
LASA issues were also reported from the hospital setting, where ePHEDrine was mistaken for epinephrine when medication vials were being re-stocked.
Practice Tip:
Recommendations to prevent mix-ups between epinephrine and ePHEDrine include use of TALLman lettering throughout the medication-use system and avoidance of side-by-side storage of the 2 products. 13
The following manufacturing deficits (which have since been addressed by the manufacturers), among others, were reported in the analysis:
- placement of the wrong bar code on an epinephrine product
- use of the same Drug Identification Number (DIN; used for verification in pharmacy processes) for both English and French Allerject products, which led to provision of a voice-enabled device (intended to walk the user through the administration process) in an incorrect language
- confusion in interpreting ratio expressions for
epinephrine concentration appearing on labels
CONCLUSION
Epinephrine is a critical, life-saving treatment for anaphylaxis that can be administered by both healthcare professionals and the general public. Because anaphylaxis can occur anywhere, workers in all healthcare sectors are encouraged to review the information identified in this analysis and implement the recommendations in this bulletin to optimize the safe and correct use of epinephrine.
The Canadian Medication Incident Reporting and Prevention System (CMIRPS) is a collaborative pan-Canadian program of Health Canada, the Canadian Institute for Health Information (CIHI), the Institute for Safe Medication Practices Canada (ISMP Canada) and Healthcare Excellence Canada (HEC). The goal of CMIRPS is to reduce and prevent harmful medication incidents in Canada.
Funding support provided by Health Canada. The views expressed herein do not necessarily represent the views of Health Canada.
The Healthcare Insurance Reciprocal of Canada (HIROC) provides support for the bulletin and is a member owned expert provider of professional and general liability coverage and risk management support.
The Institute for Safe Medication Practices Canada (ISMP Canada) is an independent national not-for-profit organization committed to the advancement of medication safety in all healthcare settings. ISMP Canada’s mandate includes analyzing medication incidents, making recommendations for the prevention of harmful medication incidents, and facilitating quality improvement initiatives.
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