Epinephrine autoinjectors: Compression and propulsion do have a role in delivery depth
2015; Elsevier BV; Volume: 3; Issue: 5 Linguagem: Inglês
10.1016/j.jaip.2015.05.024
ISSN2213-2201
Autores Tópico(s)Allergic Rhinitis and Sensitization
ResumoI read with interest the article "The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectors" by Diacono et al.1Diacono D. Pumphrey R.S. Sharma V. Arkwright P.D. The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectors.J Allergy Clin Immunol Pract. 2015; 3: 297-299Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar There are some limitations worth noting. Diacono et al compared her study with that of Song et al2Song T.T. Merrill N.L. Cole J.W. Delivery depth of epinephrine by auto-injector into the subcutaneous tissue of pig.Ann Allergy Asthma Immunol. 2013; 111: 143-145Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar published earlier. We published an in vivo study in pig thighs that showed that the subcutaneous tissue depth (SCTD) delivery of epinephrine was 2.78 ± 0.59 cm (range, 2-4 cm) with P < .0001 (1-sample t test).2Song T.T. Merrill N.L. Cole J.W. Delivery depth of epinephrine by auto-injector into the subcutaneous tissue of pig.Ann Allergy Asthma Immunol. 2013; 111: 143-145Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar The SCTD extended 94.4% beyond the length of the autoinjector needle. Based on our data, all epinephrine injections in this study diffused through tissue beyond the autoinjector's needle length of 1.43 cm. Diacono et al state "that the intramuscular injections observed in their study are not because of propulsion of fluid through the subcutaneous tissue or because of compression of the subcutaneous tissue, but rather because of the thin skin to muscle depth (STMD) in their porcine tissue model." I respectfully disagree with this assumption by Diacono et al that the reason that all our injections reached the intramuscular (IM) space was due to the thin subcutaneous (SC) fat. The purpose of our article was to show that the epinephrine is not deposited at the tip of the needle, but it is rather dispersed beyond the needle length. How can epinephrine be delivered beyond 1.43 cm or beyond the needle tip if it was not for other factors such as propulsion? There is no doubt that propulsion plays a role in reducing the effect of SCTD, thus ultimately resulting in an increased depth of delivery regardless of thin SCTD. Of most importance is the fact that epinephrine autoinjectors have a tightly coiled spring. This helps propel the epinephrine. For example, Epipen 0.30 mg has a spring force of 22.7 lb, whereas Epipen 0.15 mg has a spring force of 23.6 lb.3Wilmot JG, Shukla RB, Mahadevan L. US Patent Application 2012/0101475 A1. Meridian Medical Technologies, Inc, Columbia, Md (US) 12/909, 070 Oct 21, 2010.Google Scholar In other words, the minimum combination of pounds applied to trigger the autoinjector plus the spring force is 2 + 23 lb or about 25 lb. In a state of high anxiety and panic during anaphylaxis, the amount of pounds or Newtons applied will most likely be higher. In addition, to activate the epinephrine autoinjector, 2 to 8 lb of pressure or 9 to 35 N must be applied to the device. When we teach patients how to use the epinephrine autoinjector with a trainer, it is clearly visible that compression of the SC tissue of the thigh occurs. If no compression is applied, the autoinjector cannot be activated. The concept that there is no compression of tissue with epinephrine autoinjector is false. We believe that compression and propulsion of the autoinjector help deliver epinephrine beyond the needle length. Hypothetically, let us agree with Diacono et al's article that compression and propulsion have a lesser role than previously reported. Diacono et al state that "if the EAI needle orifice only penetrates into subcutaneous tissue, fluid is prevented from entering the muscle by the intervening deep fascia." Yet, fascia is a vascular structure. There is diffusion and absorption into the vasculature circulation once epinephrine is injected. Simons et al4Simons F.E.R. Gu X. Simons K.J. Epinephrine absorption in adults: intramuscular versus subcutaneous injection.J Allergy Clin Immunol. 2001; 108: 871-873Abstract Full Text Full Text PDF PubMed Scopus (382) Google Scholar, 5Simons F.E. Roberts Jr., Gu X. Simons K.J. Epinephrine absorption in children with a history of anaphylaxis.J Allergy Clin Immunol. 1998; 101: 33-37Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar measured peak plasma epinephrine concentration, Cmax, and time to peak plasma epinephrine concentration, Tmax, in healthy adults and children. The studies compared the pharmacokinetics and pharmacodynamics of epinephrine administered by the SC (in the arm) and the IM (via the deltoid and the vastus lateralis muscle) routes. IM administration (via the vastus lateralis, but not the deltoid) results in quicker time to peak plasma concentration (Tmax), 8 minutes for IM in the vastus lateralis muscle vs 34 minutes for SC delivery. In other words, an SC injection of epinephrine still reached circulation despite the fascia acting as a barrier. It was just slower than the IM injection in reaching peak plasma concentration. Simons et al4Simons F.E.R. Gu X. Simons K.J. Epinephrine absorption in adults: intramuscular versus subcutaneous injection.J Allergy Clin Immunol. 2001; 108: 871-873Abstract Full Text Full Text PDF PubMed Scopus (382) Google Scholar also showed that epinephrine injected in the thigh with Epipen had a higher Cmax than from the use of needle and syringe. Both modes of delivery delivered the same dose of epinephrine. The difference was the delivery method; epinephrine autoinjector uses compression and propulsion factors. Therefore, compression and propulsion do have a role in delivering epinephrine beyond the tip of the needle of epinephrine autoinjectors. The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectorsThe Journal of Allergy and Clinical Immunology: In PracticeVol. 3Issue 2PreviewEpinephrine for self-administration in anaphylaxis should be administered intramuscularly rather than subcutaneously,1-3 but in an increasing proportion of the population, epinephrine autoinjector (EAI) needles are shorter than the skin to muscle depth (STMD).4,5 The aim of this study was to investigate claims that intramuscular injection from EAI may be possible even when the needle length is less than the STMD.6-8 Full-Text PDF ReplyThe Journal of Allergy and Clinical Immunology: In PracticeVol. 3Issue 5PreviewWe thank Song1 for his interest in our article, which clearly shows that in a pig tissue model, movement of fluid from the subcutaneous tissue to the muscle is prevented by the deep fascia.2 The fact that the autoinjector spring propels the fluid from the tip of the needle with a high velocity, particularly with the EpiPen, JEXT, and Emerade, is not in doubt and is demonstrated by our and others' studies of firing a device into ballistic gelatine, porcine muscle, and subcutaneous tissue.3 As highlighted in our original article, in Song et al's experiments, skin to muscle depth refers to the distance from the surface of the skin to the methylene blue/epinephrine mixture, irrespective of which tissue planes the needle tip traversed. 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