Newsletters
November 2025

What You Need to Know

All Newsletters

​​Wrong-Route Errors Associated With Epinephrine to Treat Severe Type I Allergic Reactions

The Patient Safety Authority has received multiple reports to the Pennsylvania Patient Safety Reporting System (PA-PSRS) describing wrong-route errors with epinephrine intended to treat anaphylaxis and other severe type I allergic reactions, in which epinephrine was incorrectly ordered and/or administered by the intravenous route instead of the intended intramuscular route. We previously identified wrong-route errors as the most frequent error type involving epinephrine.1,2 Despite our published analyses and mitigation strategies,1-3 we continue to receive PA-PSRS reports describing wrong-route errors with epinephrine to treat severe type I allergic reactions.

Epinephrine is a nonselective alpha- and beta- adrenergic agonist with various indications and routes of administration.4,5 One of the indications for the use of epinephrine is the treatment of severe type I allergic reactions, including anaphylaxis. Administration of epinephrine for this indication is typically given by the intramuscular or subcutaneous route,4 with the intramuscular administration in the thigh preferred and shown to provide the highest peak blood levels.6,7 Intravenous bolus administrations of epinephrine are generally reserved for life-threatening situations such as cardiac arrest due to asystole or pulseless electrical activity.5,8 According to PA-PSRS reports, patients have experienced several adverse effects following erroneous intravenous administrations of epinephrine to treat type I allergic reactions, including sudden rise in blood pressure, electrocardiogram (EKG) changes such as ventricular tachycardia and atrial fibrillation with rapid ventricular response, “excruciating pain” and feeling of “going to die,” as well as transfer to a higher level of care.

Erroneously administered intravenous doses of epinephrine have been associated with several factors based on PA-PSRS reports, including verbal orders, lack of scanning prior to medication administration, rapid response situations, formulary change from the use of autoinjectors to the use of vials, and confusing electronic orders that lack clear and simple instructions for the route of administration. Another noteworthy aspect identified in the PA-PSRS reports is that several medications used to treat allergic reactions, such as steroids, diphenhydramine, and even famotidine, are typically administered intravenously and at the same time as epinephrine.

Facilities can mitigate the risk of wrong-route epinephrine errors by implementing the following safety strategies.

  • Use autoinjectors, which are designed to deliver premeasured single doses of epinephrine by the intramuscular or subcutaneous route.2,3,9-11
  • If not using autoinjectors, create an anaphylaxis kit that contains the vials or ampules of epinephrine, needles intended for intramuscular administration, auxiliary labels, clear instructions, and other necessary supplies.9,11 
  • Store epinephrine products used to treat anaphylaxis separately from those intended for resuscitation carts.10
  • Ensure that the order is clear, concise, and easy to understand. Do not refer to epinephrine concentrations using ratios. The U.S. Food and Drug Administration (FDA) currently requires the labeling of epinephrine strengths in amount per volume (e.g., milligrams per milliliter [mg/mL]) instead of ratio expressions (e.g., 1:1000).12
  • Distinguish the separate epinephrine orders for different indications, and ensure that the routes of administration are clearly visible.13
  • Create a warning in the automated dispensing cabinet to remind the user of the intended route of administration, and, if applicable, consider affixing auxiliary labels on the top of the cubby.13 
  • Limit the use of verbal orders to urgent situations. Create and reevaluate facility guidelines to establish standardized processes for verbal orders, such as the readback method, to confirm the route of administration.9,10 
  • Follow proper protocol in labeling and scanning the medication prior to administration.13 

References

  1. Patient Safety Authority. An Update on the “Epi”demic: Events Involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-3.
  2. Kukielka E, Jones R. Medication Safety in the Emergency Department: A Study of Serious Medication Errors Reported by 101 Hospitals From 2011 to 2020. Patient Safety. 2022;4(1).
  3. Patient Safety Authority. Let’s Stop this “Epi”demic! - Preventing Errors With Epinephrine. Pa Patient Saf Advis. 2006;3(3):16-7.
  4. National Library of Medicine. Label: EPINEPHRINE injection. Dailymed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04f07f15-55e2-411b-abb8-07eab37f5664. Published January 31, 2021. Accessed October 2025.
  5. Dalal R, Grujic D. Epinephrine. In: StatPearls [Internet]. StatPearls Publishing; 2025. Available from https://www.ncbi.nlm.nih.gov/books/NBK482160/
  6. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18_suppl_3):S829-S61. doi:10.1161/CIRCULATIONAHA.110.971069.
  7. Simons FE, Gu X, Simons KJ. Epinephrine Absorption in Adults: Intramuscular Versus Subcutaneous Injection. J Allergy Clin Immunol. 2001;108(5):871-3. doi:10.1067/mai.2001.119409; PubMed PMID: 11692118
  8. Panchal AR, Berg KM, Hirsch KG, et al. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2019;140(24):e881-e94. doi:10.1161/cir.0000000000000732; PubMed PMID: 31722552​
  9. ISMP Canada. Alert: Wrong Route Incidents With Epinephrine. ISMP Canada Safety Bulletin. 2014;14(4).
  10. ISMP Canada. Epinephrine Use for Anaphylaxis – A Multi-Incident Analysis. ISMP Canada Safety Bulletin. 2017;17(6).
  11. Institute for Safe Medication Practices. EPINEPHrine for Anaphylaxis: Autoinjector or 1 mg Vial or Ampul? NurseAdviseERR. 2016;14(1):1-4.
  12. U.S. Food and Drug Administration. Single Entity Injectable Drug Products. FDA. https://www.fda.gov/drugs/information-drug-class/single-entity-injectable-drug-products. Last reviewed June 23, 2017. Accessed October 6, 2025.
  13. Billstein-Leber M, Carrillo CJD, Cassano AT, Moline K, Robertson JJ. ASHP Guidelines on Preventing Medication Errors in Hospitals. Am J Health Syst Pharm. 2018;75:1493-617.

​

Lessons From Event Reports

Diabetes Task Force Improves Care At one facility, over a few months several incidents occurred involving patients in diabetic ketoacidosis (DKA), a life-threatening complication in which too much acid (ketones) builds up in the blood, in both the emergency department and acute care. The root cause analysis team assembled a diabetes task force to address the causes and concerns around care of diabetic patients and those in DKA. The task force,consisting of registered nurse supervisors, risk managers, the directors of Information Technology and acute care services, a diabetes educator, and the ED medical director, met over six months and implemented changes,including reviewing, revising, and creating new diabetes order sets; reviewing, revising, and creating new policies; and educating nurses and physicians of these changes. As a result of these collaborative improvements and other task force initiatives, no new incidents have ​occurred in the management of diabetes and DKA.