Abstract
BackgroundIntramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD).MethodsThis open-label, randomized, crossover study investigated pharmacokinetics and pharmacodynamics following injection of epinephrine in healthy volunteers. Individuals were stratified by maximally compressed STMD (low, < 15 mm; moderate, 15–20 mm; high, > 20 mm). Participants received epinephrine injections via EpiPen® Auto-Injector (EpiPen; 0.3 mg/0.3 mL) or IM syringe (0.3 mg/0.3 mL) at mid-AL thigh or received saline by IM syringe in a randomized order. Eligible participants received a fourth treatment (EpiPen [0.3 mg/0.3 mL] at distal-AL thigh). Model-independent pharmacokinetic parameters and pharmacodynamics were assessed.ResultsThere were numerical trends toward higher peak epinephrine concentrations (0.52 vs 0.35 ng/mL; geometric mean ratio, 1.40; 90% CI 117.6–164.6%) and more rapid exposure (time to peak concentration, 20 vs 50 min) for EpiPen vs IM syringe at mid-AL thigh across STMD groups. Absorption was faster over the first 30 min for EpiPen vs IM syringe (partial area under curve [AUC] over first 30 min: geometric mean ratio, 2.13; 90% CI 159.0–285.0%). Overall exposure based on AUC to the last measurable concentration was similar for EpiPen vs IM syringe (geometric mean ratio, 1.13; 90% CI 98.8–129.8%). Epinephrine pharmacokinetics after EpiPen injection were similar across STMD groups. Treatments were well tolerated.ConclusionsEpinephrine delivery via EpiPen resulted in greater early systemic exposure to epinephrine vs IM syringe as assessed by epinephrine plasma levels. Delivery via EpiPen was consistent across participants with a wide range of STMD, even when the needle may not have penetrated the muscle.Trial registrationsThis trial was registered with the German Clinical Trials Register (DRKS-ID: DRKS00011263; secondary ID, EudraCT 2016-000104-29) on 23 March 2017.
Highlights
Intramuscular (IM) injection of epinephrine at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis
Participants were stratified into 3 groups on the basis of STMD under maximum compression and sex
Concerns have been raised that the length of epinephrine auto-injectors may be insufficient to penetrate the muscle layer of the mid-AL thigh in patients with high STMD, which may interfere with reliable IM injection of epinephrine for treatment of acute anaphylaxis
Summary
Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. The international standard therapy for acute anaphylaxis is the prompt intramuscular (IM) injection of epinephrine in the mid-anterolateral (AL) thigh [1,2,3]. This can be achieved with the use of epinephrine auto-injectors such as EpiPen® (epinephrine injection) Auto-Injector (EpiPen; Mylan Specialty L.P., Canonsburg, PA), which delivers a bolus of epinephrine through the use of a spring-loaded cartridge [2, 4]. A previous study in a pig model demonstrated that epinephrine delivery via an auto-injector results in greater dispersion and faster uptake of epinephrine than manual delivery via syringe [4]; its implications regarding epinephrine administration via EpiPen in humans are unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
