Is there any literature that looked at use of epinephrine pens for inpatient management of anaphylaxis vs compounding epinephrine from concentrated vials?

Comment by InpharmD Researcher

The available literature does not appear to include any direct head-to-head clinical trials comparing inpatient anaphylaxis outcomes with epinephrine auto-injectors versus epinephrine compounded or manually prepared from concentrated vials. Current evidence suggests that auto-injectors may reduce preparation time, dosing errors, and administration-related mistakes by eliminating the need for dose calculation and medication preparation, whereas vial-based administration is generally less expensive but may be associated with delays and operator-dependent errors. Although simulation-based and survey studies conducted in healthcare settings have demonstrated faster administration times, fewer errors, greater provider comfort, and a strong preference for auto-injectors compared with manual preparation, these findings do not represent direct evaluations of patient outcomes in inpatient anaphylaxis management. Therefore, while available evidence supports potential workflow and safety advantages of auto-injectors, definitive conclusions regarding clinical superiority over compounded or manually prepared epinephrine in hospitalized patients cannot be made.

Background

A 2022 Wilderness Medical Society convened a panel to review the literature and develop evidence-based clinical practice guidelines on the treatment of anaphylaxis. The guideline discussed epinephrine auto-injectors (EAIs), prefilled syringes, and epinephrine manually drawn from vials or ampules, noting that auto-injectors eliminate the need to draw up medication and may reduce dosing errors, whereas vial- or ampule-based administration is less expensive but may be associated with delays and operator errors during dose calculation and preparation. The guideline concluded that device selection should be based on factors such as cost, training, and safety, but it did not compare outcomes of inpatient anaphylaxis management with auto-injectors versus epinephrine prepared from concentrated vials, nor did it evaluate pharmacy compounding practices. [1]

A 2017 scoping review comparing EAIs with epinephrine drawn into syringes identified substantial knowledge gaps and found that dosing and route-of-administration errors occurred more frequently with manually prepared epinephrine, including reports of inadvertent intravenous administration and associated adverse events. In contrast, EAIs were generally associated with fewer potentially life-threatening errors, although device-related injuries and administration mistakes were also reported. The review suggested that hospitals consider these safety and cost tradeoffs when selecting an approach but did not directly compare clinical outcomes of inpatient anaphylaxis treatment using auto-injectors versus compounded or manually prepared epinephrine. [2]

Additional hospital-focused review articles described several approaches to epinephrine storage and administration, including stocking auto-injectors, drawing doses from vials or ampules at the time of use, and maintaining pharmacy-prepared kits containing vials and administration supplies. One report described an inpatient hospital system that transitioned to epinephrine kits prepared and distributed by the pharmacy to improve speed and ease of administration, but this was based on simulation experience rather than a clinical comparison of patient outcomes. The authors also discussed compounded prefilled syringes as a potential option, noting limitations related to storage requirements and the lack of specific guidance for intramuscular use. [3], [4]

While not specific to inpatient settings, a practice parameter update published in 2023, assessed key clinical inquiries regarding the management of anaphylaxis. Preference for vials vs auto-injector pens was not discussed in detail, but regarding accessibility, the review references a 2020 study published by the Canadian Agency for Drugs and Technologies in Health. Within this study, the organization could not identify any studies that compared auto-injectors to manually administered compounded epinephrine. [5, 6]

Per a 2015 American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) practice parameter update, auto-injectors remain the preferred method for administering epinephrine to children weighing less than 15 kg (33 pounds), despite being technically off-label for this weight group. This recommendation is made because using an auto-injector is safer and provides a more accurate dose than having a caregiver draw epinephrine from a vial, a process prone to dangerous errors. The guidance is further supported by the fact that the optimal dose of epinephrine is not definitively established, making the proven safety and accuracy of an auto-injector the more prudent choice. [7]

A 2017 article explores the critical role of epinephrine in managing anaphylactic emergencies, particularly focusing on the choice between autoinjectors and 1-mg vials or ampoules. Epinephrine autoinjectors are emphasized for their accessibility and ease of use in community settings, providing a vital resource for those at risk. The article draws attention to significant risks associated with using 1-mg ampoules or vials, such as wrong-dose and wrong-route errors. The complexity of drawing up and administering a precise dose during stressful emergency situations can lead to potentially harmful consequences, including inadvertent intravenous administration. Within the context of healthcare settings, the author advocates for the deployment of epinephrine autoinjectors to mitigate these risks. Nevertheless, challenges persist, including the financial implications of stocking autoinjectors and the need for comprehensive training and retraining of healthcare professionals to ensure proper usage and readiness in the event of an anaphylactic reaction. [8]

A 2025 review mentions supporting studies that suggest intramuscular (IM) administration of epinephrine by auto-injectors is found to be substantially better at delivering therapeutically relevant doses with significantly higher plasma adrenaline compared to normal syringe injections. Despite being low-cost and low-tech, use of ampules, syringes, and training for proper needle technique can lead to struggles for prompt dosing and accuracy. Healthcare providers, in particular, demonstrated inconsistencies in epinephrine concentrations when challenged in a published study to draw doses promptly from ampoules. Extreme cases like refractory anaphylaxis may necessitate intravenous (IV) epinephrine, but would require careful supervision under skilled healthcare practitioners to monitor its effects within the hospital, rather than an outpatient clinic. [9]

Background References: [1] Gaudio FG, Johnson DE, DiLorenzo K, et al. Wilderness Medical Society Clinical Practice Guidelines on Anaphylaxis. Wilderness Environ Med. 2022;33(1):75-91. doi:10.1016/j.wem.2021.11.009
[2] Chime NO, Riese VG, Scherzer DJ, et al. Epinephrine Auto-Injector Versus Drawn Up Epinephrine for Anaphylaxis Management: A Scoping Review. Pediatr Crit Care Med. 2017;18(8):764-769. doi:10.1097/PCC.0000000000001197
[3] Brown JC. Epinephrine, auto-injectors, and anaphylaxis: Challenges of dose, depth, and device. Ann Allergy Asthma Immunol. 2018;121(1):53-60. doi:10.1016/j.anai.2018.05.001
[4] Sargel CL, Maa T. Epinephrine Auto-Injectors Versus Manually Drawn Up Epinephrine: Is There a Better Option?. Pediatr Crit Care Med. 2017;18(8):807-808. doi:10.1097/PCC.0000000000001211
[5] Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124-176. doi:10.1016/j.anai.2023.09.015
[6] Weir A, Argáez C. Epinephrine Auto-Injectors for Anaphylaxis: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Apr 24. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563019/
[7] Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. doi:10.1016/j.anai.2015.07.019
[8] Grissinger M. EPINEPHrine for Anaphylaxis: Autoinjector or 1-mg Vial or Ampoule?. P T. 2017;42(12):724-725.
[9] Ebisawa M, Muraro A, Worm M, et al. Optimizing Adrenaline Administration in Anaphylaxis: Clinical Practice Considerations and Safety Insights. Clin Transl Allergy. 2025;15(8):e70085. doi:10.1002/clt2.70085
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any literature that looked at use of epinephrine pens for inpatient management of anaphylaxis vs compounding epinephrine from concentrated vials?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


Benefit of Epinephrine Autoinjector for Treatment of Contrast Reactions: Comparison of Errors, Administration Times, and Provider Preferences
Design

Prospective study with simulation scenarios

N= 189

Objective To compare treatment of a moderate-severity reaction with intramuscular epinephrine by either the traditional manual method of drawing up and delivering epinephrine with a needle and syringe or the use of an epinephrine autoinjector
Study Groups

Manual delivery (n= 42)

Autoinjector (n= 34)

Inclusion Criteria All radiology fellows, residents, midlevel providers, and radiology nurses at the institution during September 2015
Exclusion Criteria Interventional radiologists were exempt from attending the program
Methods Participants engaged in a contrast reaction simulation program with three scenarios in a high-fidelity simulation lab. Groups were randomized to use either an autoinjector or manual delivery for IM epinephrine administration. Time to administration and errors were recorded. Surveys assessed comfort levels with each method. 
Duration September 2015
Outcome Measures Time to administration of IM epinephrine Secondary: Number of administration errors, provider comfort level
Baseline Characteristics   Manual Delivery  Autoinjector 
Nurse 19 (8%) 21 (7%)
Midlevel (PA/NP/RA) 2 (1%) 0 (0)
Resident 43 (18%) 12 (4%)
Fellow 14 (6%) 15 (5%)
Attending physician 21 (9%) 53 (18%)
Results   Manual Delivery Autoinjector p-value

Time to Intramuscular Administration of Epinephrine

Acquisition

Injection

Total administration

 

45.8 ± 31.6

62.9 ± 27.0

108.8 ± 26.2

 

23.8 ± 16.8

14.8 ± 8.1

38.7 ± 20.8

 

0.04

< 0.001

< 0.001

The autoinjector was associated with fewer errors (one error versus seven in manual delivery), and its users were more comfortable with its use. Among manual delivery sessions, errors included incorrect dosing and improper administration methods, such as subcutaneous or intravenous injection. Participants reported higher comfort levels with the autoinjector method, with 94% feeling comfortable or very comfortable using it compared to 77% with manual delivery. Additionally, 96% found the autoinjector easier to use. Previous practical experience with IM epinephrine outside of simulation was reported by 19%, with a small fraction having used an autoinjector in real situations.
Adverse Events Errors in epinephrine administration were common with manual delivery (46% of sessions), including wrong dose and method of administration. 
Study Author Conclusions Use of an epinephrine autoinjector for treatment of contrast reactions was associated with a significantly greater degree of provider comfort, shorter time to administration, and fewer errors.
Critique The study effectively demonstrated the benefits of using an epinephrine autoinjector over manual delivery in terms of time efficiency and error reduction. However, the study was limited by its focus on adult populations and the specific autoinjector device used, which was later recalled. The cost of autoinjectors compared to manual delivery systems was not addressed in terms of feasibility for widespread implementation.
Table 1 References:
[10] Asch D, Pfeifer KE, Arango J, et al. JOURNAL CLUB: Benefit of Epinephrine Autoinjector for Treatment of Contrast Reactions: Comparison of Errors, Administration Times, and Provider Preferences. AJR Am J Roentgenol. 2017;209(2):W363-W369. doi:10.2214/AJR.16.17111

Autoinjectors Preferred for Intramuscular Epinephrine in Anaphylaxis and Allergic Reactions
Design

Observational study using a Web-based survey

N= 172

Objective To examine healthcare providers’ preferences and perceptions about the optimal mode of epinephrine delivery with respect to safety, effectiveness, ease of administration, convenience, and cost for the two methods of epinephrine administration in management of anaphylaxis and allergic reactions
Study Groups All participants (n= 172)
Inclusion Criteria Healthcare providers including ED pharmacists, emergency medicine residents, ED physician assistants, ED nurse practitioners, ED nurses, and ED staff physicians at Mayo Clinic Hospital - Rochester, Saint Marys Campus
Exclusion Criteria Not specified
Methods A Web-based survey was conducted among ED healthcare providers to assess their perceptions and preferences regarding the use of epinephrine autoinjectors versus manual injection for anaphylaxis and allergic reactions. The survey included questions on ease of use, convenience, satisfaction with weight-based dosing, risk of dosing errors, cost to patient, speed of administration, and risk of self-injury. Responses were collected anonymously and analyzed statistically.
Duration Survey conducted between April 28 and June 16, 2011
Outcome Measures Ratings on ease of use, convenience, satisfaction with weight-based dosing, risk of dosing errors, cost to patient, speed of administration, and risk of self-injury
Baseline Characteristics   All (n=172)
Female 96 (57%)

Years in practice

0-3

4-9

10-20

>20

 

24 (14%)

49 (28%)

52 (30%)

47 (27%)

Results   Epinephrine autoinjector Manual IM injection p-value
Ease of use 85.5 ± 16.4 49.6 ± 24.7 <0.001
Convenience 88.7 ± 15.0 38.2 ± 26.3 <0.001
Satisfaction with weight-based dosing 68.3 ± 23.5 56.7 ± 25.8 <0.001
Risk of dosing errors 20.1 ± 19.8 67.8 ± 22.0 <0.001
Cost to patient 58.2 ± 15.9 40.6 ± 16.9 <0.001
Speed of administration 84.1 ± 16.6 45.7 ± 23.3 <0.001
Risk of self-injury 52.6 ± 24.8 38.4 ± 22.4 <0.001
82% of respondents preferred the autoinjector over manual injection for epinephrine administration, citing advantages such as reduced training time, ease of use, and decreased risk of dosing errors (p<0.001 for all comparisons).
Adverse Events Three participants (2%) reported a finger stick injury from an epinephrine autoinjector.
Study Author Conclusions ED healthcare providers preferred the autoinjector method of IM epinephrine administration for the management of anaphylaxis or allergic reactions. Epinephrine autoinjector use may reduce barriers to epinephrine administration for the management of anaphylaxis in the ED.
Critique The study had a high response rate and provided valuable insights into provider preferences for epinephrine administration methods. However, only 28% of respondents had experience with both methods, which may limit the generalizability of the findings. Additionally, the study was conducted at a single tertiary care ED, which may not reflect practices in other settings. The potential for recall bias exists due to the time gap between the introduction of autoinjectors and the survey.
Table 2 References:
[11] Campbell RL, Bellolio MF, Motosue MS, Sunga KL, Lohse CM, Rudis MI. Autoinjectors Preferred for Intramuscular Epinephrine in Anaphylaxis and Allergic Reactions. West J Emerg Med. 2016;17(6):775-782. doi:10.5811/westjem.2016.8.30505