Clinical Communications

The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectors

The variation of needle lengths of epinephrine auto-injectors (EAIs) has not been investigated.

To investigate the impact of the variation of the needle length of EAIs.

Skin-to-muscle (STMD) and skin-to-bone distances (STBD) were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, applying high or low pressure on the probe. The risk of subcutaneous and periosteal/intraosseous injection was calculated using the lower and upper acceptance limits for length of EAI needles as provided for 3 high-pressure EAIs (HPEAI) and 1 low-pressure EAI (LPEAI).

The variation in needle length of the HPEAIs are for Epipen Jr/Epipen 5 mm, for Jext 2 mm, for Auvi-Q 2.5 mm, and for the LPEAI, Emerade, 1.5 mm. When using the longest acceptable needles for Epipen Jr, the risk of intraosseous/periosteal penetration was highest in children weighing less than 15 kg at 60% and for Jext at 43%. The risk was low for Auvi-Q and Emerade. The risk of subcutaneous injection was greatest with the shortest needles of the Auvi-Q 0.1 mg at 94% in children weighing less than 15 kg. In adults, the risk of subcutaneous injection using the shortest needles was for Epi-Pen at 41%, Jext at 36%, Auvi-Q at 38%, and Emerade at 12%.

The variation in needle length of EAIs influences the risk of subcutaneous and intraosseous/periosteal injections. Compared with Epipen Jr, the Auvi-Q 0.1 mg for children weighing less than 15 kg had a low risk of intraosseous/periosteal injection but a very high risk of subcutaneous injection. For adults, there is a significant risk of subcutaneous injection.

To summarize evidence supporting the use of point-of-care ultrasonography as a clinical tool for allergists and immunologists.

Cochrane Library, Medline, EMBASE, and Scopus databases were searched for articles published before December 18, 2018.

We included any retrospective or prospective study that evaluated ultrasonography in allergy and immunology and epinephrine autoinjector (EAI) needle length.

The standard EAI needle length may be inadequate for intramuscular delivery of epinephrine, particularly for women, at risk of anaphylaxis. In patients who weigh less than 15 kg, the lengths of commercially available EAIs may be too long, risking inadvertent intraosseous injection and resultant complications. Ultrasonography can be routinely used in the allergy clinic to guide needle length and angle for subcutaneous allergen immunotherapy injections to minimize systemic adverse effects.

Point-of-care ultrasonography can be a useful tool to enhance patient care and safety in an allergy clinic. Ideally, all patients prescribed EAIs should have ultrasonographic measurement of the skin to muscle distance and skin to bone distance to assist in identifying patients at risk of subcutaneous or intraosseous injection in anaphylaxis and those at risk of intramuscular injection during subcutaneous allergen immunotherapy injections.

Le traitement de l’anaphylaxie en pratique courante repose, en première ligne, sur l’utilisation sans délai de l’adrénaline par voie intramusculaire. Les auto-injecteurs d’adrénaline permettent une injection dans des conditions d’efficacité et de sécurité optimales, mais dans une gamme de doses restreinte, entre 0,15 et 0,50 mg, par injection. Toutes les recommandations internationales sur le traitement de l’anaphylaxie en pratique courante valident une même posologie d’adrénaline de 0,01 mg/Kg de poids par injection intramusculaire (dose maximale de 0,5 mg par injection) malgré l’absence d’étude de qualité sur ce thème. Cette mise au point du groupe de travail « Anaphylaxie » de la Société française d’allergologie analyse les données actuelles concernant le traitement par adrénaline avec les auto-injecteurs, en insistant sur la problématique de la posologie.

Intramuscular adrenaline is the first-line treatment for anaphylaxis. Adrenaline auto-injectors allow injection under conditions of optimal efficacy and safety, but commercially available formulations are restricted to a dose range of 0.15 and 0.50 mg per injection. All the international anaphylaxis guidelines recommend the administration of intramuscular adrenaline at a dose of 0.01 mg/Kg of body weight, with a maximum dose of 0.5 mg per injection, despite the lack of evidence-based data. This position statement, prepared by the Anaphylaxis working group of the French Allergology Society, attempts to analyse current data regarding the use of adrenaline auto-injectors as treatment of anaphylaxis with, in particular, emphasis on the dosage issue.

This review was undertaken to review epinephrine dosing, site and route of administration, focusing on special populations (patients weighing less than 15 kg, and obese patients); and to discuss storage and delivery of epinephrine in prehospital and hospital settings.

Review of published literature.

Relevance.

The recommended 0.01-mg/kg (maximum 0.3–0.5 mg) epinephrine dose in anaphylaxis is based on limited pharmacokinetic data in healthy volunteers. No pharmacokinetic or pharmacodynamics studies involving patients in anaphylaxis have been published. When epinephrine auto-injectors (EAIs) are used in infants, the dose increasingly exceeds the recommended dose as weight decreases, although the clinical significance of this is unclear. Limited data indicate that the intramuscular route and lateral thigh site are superior. Ultrasound studies suggest that 0.15 EAI needles may be too long for many patients weighing less than 15 kg, and 0.3 mg EAI needles may be too short for obese patients weighing more than 30 kg. A newly available 0.1 mg EAI has a lower dose and shorter needle better suited to patients weighing 7.5 to 15 kg. In some medical settings, vials and syringes may provide a safe, efficient alternative with substantial cost savings over EAIs.

EAIs should be available in the community with doses and needle depths that meet the needs of all patients. More research on epinephrine pharmacodynamics are needed in children and adults in anaphylaxis, to better delineate what optimal doses should be. Optimizing epinephrine dose and delivery has the potential to improve anaphylaxis outcomes and prevent adverse events.

Epinephrine should be administered intramuscularly in the anterolateral aspect of the thigh. The length of the epinephrine auto-injector (EAI) needle should ensure intramuscular injection.

To discuss suitable EAI needle lengths based on ultrasound measurements related to weight.

The skin-to-muscle distance (STMD) and skin-to-bone distance (STBD) were measured by ultrasound in the mid-third of the anterolateral area of the right thigh when applying high pressure (8 lb; high-pressure EAI [HPEAI]) or low pressure (low-pressure EAI [LPEAI]) on the ultrasound probe. The study included 302 children and adolescents and 99 adults. The maximum and minimum STMD and the maximum and minimum STBD were estimated.

Using HPEAIs, the risk of periosteal or intraosseous penetration was 32% in children weighing less than 15 kg. The risk of subcutaneous injection was 12% in adolescents and 33% in adults. With LPEAIs, there was no risk of periosteal or intraosseous injection and the risk of subcutaneous injections in adolescents and adults was lower at 2% and 10%, respectively. A new EAI for injection in small children would have no risk of periosteal or intraosseous injection but would have 71% chance of subcutaneous deposit of epinephrine.

Common HPEAIs have a high risk of periosteal or intraosseous penetration in children and subcutaneous injections in overweight and obese adults. LPEAIs have some risk of subcutaneous injection in adults. HPEAIs with 0.1 mg of epinephrine and shorter needles have no risk of periosteal or intraosseous injection but have a high risk of subcutaneous deposit. For adult or overweight or obese patients, HPEAIs and LPEAIs should have longer needles. Future studies should focus on triggering pressures and variations in needle length.

Food allergy and anaphylaxis appear to be increasing in the United States, especially in young children, and preparedness is paramount to successful emergency management in the community. Although the treatment of choice for anaphylaxis is epinephrine delivered by autoinjection, some devices are challenged by less user-friendly designs or pose the risk of injury, especially in young patients. Human factors engineering has played a larger role in the development of more recent epinephrine autoinjector technologies and will continue to play a role in the evolution and future design of epinephrine autoinjectors.

To discuss contemporary issues related to the identification and management of anaphylaxis, current and future epinephrine autoinjector design, and unmet needs for the treatment of special populations, namely, young children weighing less than 15 kg.

The literature was reviewed and select articles retrieved to support expert clinical opinions on the need for improved recognition of anaphylaxis, epinephrine autoinjector design, and unmet needs in special populations.

Anaphylaxis may be underrecognized and poorly defined in infant- and toddler-aged children, current devices may not be adequate to safely treat these patients (ie, inappropriate needle length), and health care professionals may not be aware of these issues.

As epinephrine autoinjector technology continues to evolve, device characteristics that promote safe, user-friendly experiences and give clinicians and their patients confidence to successfully treat anaphylaxis during an emergency, without injury, will be favored.