Information for healthcare professionals in Sweden only.

Cartridge vs syringe auto-injectors: a misleading discussion

by Rafael Ferrandiz, Ph.D. on September 16, 2014

Summary: The intramuscular delivery of adrenaline is determined by the needle length, not the basic mechanism of the adrenaline auto-injectors.

Anaphylaxis is one of the conditions that demand a self treatment as soon as the symptom appears. Adrenaline auto-injectors (AAIs) offer immediate treatment and, therefore, avoid risk of incorrect dosing inherent to the use of an ampoule and a syringe [1].

AAIs use 2 injection systems:

• cartridge: used by EpiPen, Jext, Auvi-Q/Allerject.
• syringe: used by Emerade, Adrenaclick, Twinject and Anapen.

In the cartridge system, the adrenaline solution is filled into the cartridge and the needle is not attached to the glass body. The firing mechanism, e.g. a spring or pressurized gas, moves the cartridge toward the needle. One end of the needle then penetrates the rubber closure of the cartridge and they move forward together. The needle penetrates the tissue while the piston empties the dose.

In the syringe system, the adrenaline solution is contained in the syringe and the needle is fixed to the glass body. The firing mechanism, e.g spring, moves the whole syringe forward to then penetrate the tissue. The piston empties the dose. (Fig1)

Fig. 1. The syringe has a fixed needle, whereas the cartridge needle is separate from the glass body.

It has been suggested that cartridge-based AAIs may be better able to rapidly deliver a dose of intramuscular adrenaline than syringe based systems [2]. This theory is misleading with regard to both the speed and route of the injection.

All AAIs are unique

The misleading theory is based singularly on work by Schwirtz and Seeger [2]. In this study they used Anapen as the only comparator syringe system. Anapen has a weak injection spring and a short needle, specific to the design of Anapen.This design is recognised as not representative of syringe-based autoinjectors. Quite simply, a study comparing Epipen, Jext and Anapen cannot be used to generalise differences between the systems.

Similarly, Frew [3] made a general description of the syringe system, but he also used Anapen as the only comparator, drawing similar conclusions to the Schwirtz and Seeger study. His general conclusions regarding safety issues and penetration depth are not representative of other syringe-based AAIs.

The speed of injection is decided by the injection force

The mechanisms behind the cartridge or syringe systems determine how the injection and, therefore, delivery of the dose occur. In both systems, the speed of the piston depends on the strength of the springs (or other power source). The springs may be strong or weak in both systems.

• Anapen is based on an insulin pen with a weak spring.
• EpiPen has a 50 year old technique with a strong spring developed for the American army. A similar mechanism is found in Jext.
• Auvi-Q has a spring and pressurized gas that drive the mechanism.
• Emerade has an advanced 3 spring technology: One spring moves the syringe with the needle to penetrate the muscle. A second spring delivers the dose after the needle is fully inserted. The third spring is dedicated to the protective needle cover following use.

Emerade, Auvi-Q, Adrenaclick and Twinject were specially developed for anaphylaxis treatment with adrenaline.

Jet force does not penetrate fascia

It has also been suggested that the jet force of AAIs may generate a deeper injection than the needle tip [4, 5]. The results obtained from ballistic gel are misleading because dispersal of fluid injected into gelatine does not represent dispersal in tissues with complex structure [6].

It has been demonstrated that, despite the high pressure generated by the plunger with some AAIs and high jet velocity, the actual pressure at the needle-tip is low during injection. The jet force is similar for Emerade, Jext and Epipen and lower in Anapen. The expulsion force generated by strong springs has no effect on IM delivery of adrenaline [6].

To achieve an IM injection the needle needs to reach the muscle. If the needle does not penetrate the connective tissue and reach the muscle, an injection occurs in the subcutaneous fat layer [6, 7].

Pumphrey et al also showed that a longer needle in the AAIs gives a deeper injection [6].

The ideal AAI can be met by both systems

The criteria for the ‘ideal’ AAI was summarised by Frew in 2011 [3]. It should:

1. deliver adrenaline to the correct tissue compartment.
2. deliver adrenaline within the correct timeframe.
3. deliver the correct dose of adrenaline.
4. be robust and reliable enough to withstand real life use.
5. be easy, convenient and safe for patients or carers to use.

None of these features are unique for cartridge-based AAIs and both syringe and cartridge systems can fulfil this criteria. It is the inherent design, the performance characteristics, the selection of doses and the needle lengths that make an AAI suitable for the treatment of anaphylaxis not whether the delivery system is syringe or cartridge.

Conclusions

The mechanisms behind the delivery of adrenaline in AAIs are very different. These vary from relatively simple to very sophisticated. Different systems do have some impact on AAIs performance, but it is misleading to generalise that one system is more reliable or robust than the other. It is the needle length and injection force, not simply the mechanism which determines a successful IM injection.

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 are needed to reach the muscle with adrenaline auto-injectors

Low risk of over-penetration by adrenaline auto-injectors

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References

1. Simons, F.E.R., Chan, E.S., Gu, X., Simons, K,J., Epinephrine for the out-of-hospital (first aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical? J Allergy Clin Immunol, 2001. 108: p. 1040-4.
2. Schwirtz, A. and H. Seeger, Are adrenaline autoinjectors fit for purpose? A pilot study of the mechanical and injection performance characteristics of a cartridge-versus a syringe-based autoinjector. J Asthma Allergy., 2010. 3: p. 159-67.
3. Frew, A.J., What are the 'ideal' features of an adrenaline (epinephrine) auto-injector in the treatment of anaphylaxis? Allergy, 2011. 66: p. 15-25.
4. Schwirtz, A. and H. Seeger, Comparison of the robustness and functionality of three adrenaline auto-injectors. J Asthma Allergy., 2012. 5: p. 39-49. Epub 2012 Aug 20.
5. Song, T.T., N.L. Merrill, and J.W. Cole, Delivery depth of epinephrine by auto-injector into the subcutaneous tissue of pig. Annals of Allergy, Asthma & Immunology, 2013. 111(2): p. 143-145.
6. Pumphrey, R., Diacono, D., Sharma, V., Arkwright, P.D., Tissue distribution of dye marker following autoinjector use. EAACI Congress, Copenhagen, 2014(Poster 367).
7. Pumphrey, R., Do 'EpiPens' save lives? Meet the Expert 16 , EAACI 2011, Istambul, 2011.