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Information for healthcare professionals in Sweden only.

Low risk of over-penetration by adrenaline auto-injectors

The needles are too short, not too long

by Rafael Ferrandiz, Ph.D. on March 17, 2016

Summary: A longer needle increases the chance of an intramuscular injection in more patients. In the unlikely event of the needle reaching the bone, the benefit of an appropriate IM injection, under a life threatening episode, overcomes this small risk.

Intramuscular injection is recommended for fast adrenaline effect, however, the needles in some currently available adrenaline auto-injectors (AAI) are too short to reach the thigh muscle in many patients. [1-5] A longer needle ensures an IM injection in larger groups of patients who would be at risk of undertreatment with shorter needles.

The development of a new AAI with a longer needle raises the question of risk of bone injury. However, as stated, the main problem with adrenaline auto-injector needles is they are too short, not too long.

Over-penetration is a minor problem

Over-penetration may cause pain and/or damage to the bone periosteum in patients who receive vaccination. However, the potential for needle over-penetration beyond intramuscular level into the bone or periosteum has been given little examination because of its perception as being a minor problem [6].

The skin-to-bone distance (STBD) over the anterolateral aspect of the thigh was reported both in infants (9-27 weeks) and toddlers (68-88 weeks) to be 17 mm [7]. Similarly, in a study of optimal intramuscular needle penetration, Lippert et al [6] investigated the distance to bone in thighs of children from 2 months to 6 years of age. The results showed that the sum of mean measurements of subcutaneous fat and muscle thickness for the thigh were larger than 25 mm in both boys and girls (Table 1).

Age Fat Thickness
± SD, mm
Muscle Thickness
± SD, mm
Fat Thickness
± SD, mm
Muscle Thickness
± SD, mm
1-12 mo 14.65 ±3.76 18.83 ±3.51 10.98 ±2.77 15.33 ±2.39
1-2 y 11.36 ±5.51 19.40 ±5.28 12.23 ±5.54 20.87 ±6.00
3-6 y 13.00 ±6.10 25.04 ±8.29 11.32 ±4.76 24.76 ±4.39

Table 1. Fat (subcutaneous) and muscle layer thickness measurements for thigh muscle in both female and male patients arranged by age according to CDC recommendations (adapted from [6])

At these early ages over-penetration of the thigh muscle would occur in only 11 of 100 children with a 25 mm needle. This supports the conclusion that a 22.2-25.4 mm needle is suitable for thigh intramuscular injections in both genders of infants and children up to age 6 years. This is in line with the recommendations from the U.S. Centers of Disease Control (CDC) [8] and the UK Resuscitation Council Guidelines that recommend the use of short 16 mm needles for small infants only [9].

A recent study from Canada [10] investigated the risks of bone hitting and subcutaneous injection by EpiPen/EpiPen Jr, Auvi-Q (Allerject), Jext and Emerade, when simulating their administration in children and adolescents at risk of food anaphylaxis.

Taking into consideration existing studies on infants and children, the risk of over-penetration and bone hit is very low with a 16 mm needle in patients weighing less than 30 kg, as well as in patients weighing more than 30 kg with a 23 mm needle.

The dose is delivered IM if the needle reaches the bone

There are two hypothetical scenarios related to the unlikely event that a needle reaches the bone:

a) The needle penetrates the bone

Even in the improbable case that the injection of adrenaline reaches the bone, there is minimal risks of damage.

Adrenaline has been used in intraosseous (IO) route. The IO route has been an established technique in pediatric emergency care for more than 3 decades [11]. Placing an intravenous line in patients during cardiac arrest while CPR is being per­formed is difficult and sometimes not possible. One approach to earlier administration of adrenaline during out-of-hospital cardiac arrest is via the IO route, as this can be performed quickly in the field. A favorable neurological outcome was demonstrated with early IO compared with later IV adrenaline. For these reasons, IO adrenaline is recommended [12-14]. Drugs containing adrenaline are also used by IO route in anesthetics, especially in the field of deontology [15, 16].

Certainly IV or IO adrenaline is reserved for severe, life-threatening anaphylaxis with associated hypotension, airway swelling, severe bronchospasm or inadequate response to intramuscular adrenaline. The strengths of 0.15 and 0.3 mg in the AAIs are 50 to 100 times the concentration suggested for IO infusion, respectively. But importantly, there are no studies to confirm that the AAIs would penetrate through the femur of children [10]. The injection of medicines into the bone requires special techniques and devices. The risk of damage by IO adrenaline can therefore consider being negligible.

b) The needle is partially damaged preventing the delivery of the adrenaline dose

When investigating the physical resistance of the needle of Emerade in the event of a bone hit, it was found that the needle slightly deformed but did not penetrate the bone and the injection occurs outside. Based on the results it is considered unlikely that the deformation of the needle tip would have any impact on the injection time/flow [17].


In life threatening anaphylaxis, the use of a long needle to ensure IM injection overcomes all potential risk of bone injury.

Read more

Emerade adrenaline auto-injector has a longer needle, 25 mm for 500 and 300 micrograms, 16 mm for 150 microgram [22].

Longer needles needed to reach the muscle with adrenaline auto-injectors

Cartridge vs syringe auto-injectors: a misleading discussion

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  1. Song, T.T., Nelson, M.R., Chang, J.H., Engler, R.J.M., and Chowdhury, B.A., Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues. Ann Allergy Asthma Immunol, 2005. 94: p. 539-42.
  2. Stecher, D., et al., Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly? Pediatrics., 2009. 124(1): p. 65-70.
  3. Bhalla, M.C., et al., Predictors of epinephrine autoinjector needle length inadequacy. Am J Emerg Med, 2013. 31(12): p. 1671-6.
  4. Bewick, D.C., et al., Anatomic and anthropometric determinants of intramuscular versus subcutaneous administration in children with epinephrine autoinjectors. The Journal of Allergy and Clinical Immunology: In Practice, 2013. 1: p. 692-694.
  5. Hobbins, S., Johnstone, J., O’Hickey, S., Subcutaneous tissue precludes intramuscular injection in the majority of patients prescribed epinephrine auto injectors. 2014 EAACI Congress, Copenhagen. Poster 698, 2014.
  6. Lippert, W.C. and E.J. Wall, Optimal intramuscular needle-penetration depth. Pediatrics., 2008. 122(3): p. e556-63. Epub 2008 Aug 11.
  7. Groswasser, J., et al., Needle length and injection technique for efficient intramuscular vaccine delivery in infants and children evaluated through an ultrasonographic determination of subcutaneous and muscle layer thickness. Pediatrics, 1997. 100(3 Pt 1): p. 400-3.
  8. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W, W.S., Hamborsky J, eds., Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book. Appendix D. Vaccine administration guidelines. 2012. 12th ed. Washington DC.
  9. Resuscitation Council, U.K., Emergency treatment of anaphylactic reactions. Guidelines for healthcare providers. 2008, Resuscitation Council (UK): London. p. 50 pp.
  10. Dreborg, S., et al., Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy? Allergy Asthma Clin Immunol, 2016. 12: p. 11.
  11. Zuercher, M., et al., Epinephrine improves 24-hour survival in a swine model of prolonged ventricular fibrillation demonstrating that early intraosseous is superior to delayed intravenous administration. Anesth Analg., 2011. 112(4): p. 884-90. Epub 2011 Mar 8.
  12. Attaran, R.R. and G.A. Ewy, Epinephrine in resuscitation: curse or cure? Future Cardiol., 2010. 6(4): p. 473-82.
  13. Neal, C.J. and D.F. McKinley, Intraosseous infusion in pediatric patients. J Am Osteopath Assoc., 1994. 94(1): p. 63-6.
  14. de Caen, A.R., A. Reis, and A. Bhutta, Vascular access and drug therapy in pediatric resuscitation. Pediatr Clin North Am., 2008. 55(4): p. 909-27, x.
  15. Sixou, J.L. and M.E. Barbosa-Rogier, Efficacy of intraosseous injections of anesthetic in children and adolescents. Oral Surg Oral Med Oral Pathol Oral Radiol Endod., 2008. 106(2): p. 173-8. Epub 2008 Apr 18.
  16. Meechan, J.G., The use of the mandibular infiltration anesthetic technique in adults. J Am Dent Assoc., 2011. 142(Suppl 3): p. 19S-24S.
  17. SHL, report 0162-000-TR-S013 (1.0)
  18. Emerade, solution for injection in pre-filled pen. Summary of Product Characteristics, SmPC UK. 2014.