viz Epipen, Jext, Emerade, AUVI-Q etc.

Who needs one?  Anyone at risk of anaphylaxis, is the simple answer.  But there are no reliable ways of identifying who is at risk of anaphylaxis!

There is also a big problem with them not being used even when they are available.

Who needs one?

EAACI position paper – see Anaphylaxis management.  Only a couple of absolute indications, otherwise a risk assessment. 

2021 Expert working group – MHRA set up after further coroner’s inquests into anaphylaxis deaths, following European safety review in 2015.  Recommendations are:

• Early adrenaline.  Which means teaching families/children recognition of signs. 
• Need for 2 pens emphasized.
• Brand specific training
• Key messages on packaging eg “don’t delay”, “use second pen if necessary”
• Posture detailed – “lie down with legs up”, “sit up if breathing difficult but don’t change position suddenly”, “stay lying down [regardless of whether you feel better or what people tell you to do]” 
• Wider availability of AAIs in public places likely to be beneficial but this would require legislative amendment as well as public training, and concerns about storage conditions and supply would need to be addressed.
• Dosing errors in hospital common, but given pressure on AAI supply may not be great solution. Other solutions would be labelled kits, pre-filled syringes, different system of labelling adrenaline (!).
• Reporting of device related adverse events, and anaphylaxis events (including re-establishment of fatal anaphylaxis registry).

Technique

Patient should lie down (but if respiratory symptoms then may be more comfortable sitting). Video available at Epipen and Jext websites. 3 minute training video with more explanation on Youtube. Or scan this:

• Remove safety cap (Blue for Epipen, Yellow for Jext).
• Hold in fist, avoid touching ends to reduce risk of accidental self injection.
• Jab orange (Epipen) or black (Jext) tip firmly into upper outer thigh, through clothing if necessary but avoid seams and pocket contents eg coins, mobiles – clicks as it activates.
• Hold for 3 secs (Epipen), 10 secs (Jext).
• Previous advice was to rub area (probably now white) vigorously for 10 seconds. Adrenaline causes vasoconstriction in skin, but vasodilatation in muscle so should be absorbed as long as IM.  Not specified now.
• Phone 999.
• Dispose of device safely (device is self sheathing).  Note that some drug left behind, which is normal, and that pen cannot be reused!).
• Repeat after 5 minutes if necessary. Use a different leg!

Training checklist (from GOS):

• When to use it
• How to use it
• When to carry it ie at all times!
• Storage/disposal – should be protected from heat and light
• Expiry date – reminder service available from support website (link above)
• Friends/babysitters aware?
• School aware?
• School trained and have pen?
• Medicalert bracelet/watch/necklace – other brands available

They come in two different doses – standard strength is 0.3 mg, there is  a 0.15 mg strength prescribed for younger children (15-30kg). Emerade (not currently available) gcomes in a 0.5mg strength for adults and children over 12, which is a more appropriate dose for bigger people viz over 60kg.

If patient is under 15kg,  CYANS guidance is that over 7.5kg, the potential benefit outweighs the risk.  For those under 7.5kg, need to balance risk of anaphylaxis with risk of drug error from drawing up adrenaline from vial with syringe and needle.

Epipen has 18 month shelf life, self sheaths, and has a window to show ready to use. Blue safety cap, orange needle end. JEXT pen similarly self sheathing, coloured window to show whether it is live or not, 24 months shelf life. Yellow safety cap, black needle end. Same needle length.

Anapen has been discontinued.  Had a shorter needle, different technique – remove caps from both ends, hold against leg, put your thumb over the end and press red button.

Emerade pen has safety cap over needle end – this is different from the other types but is logically simpler. Needle is 25mm long cf 15mm Epipen/Jext.  Currently off market due to reliability of activation concerns.

Number of Pens

2018 MHRA review recommends 2 pens available at all times, and made the recommendation directly to families so they can demand them from their doctor!  BSACI (2016) suggested children should in most cases just get 2 pens, 1 for home and 1 for school, but this was contradicted by later European Medicines Agency (EMA) and previous NICE guidance.  Still not clear why they should ever by prescribed in single rather than twin packs…

European medicine agency review (legally binding in EU) concluded that:

• due to uncertainties about the site of drug delivery and the speed of adrenaline action within the body, it is recommended that healthcare professionals prescribe 2 auto-injectors, which patients should carry at all times
• the needle length of the device is now stated in the product information because this may be an important factor for the prescriber to consider when choosing a suitable auto-injector
• the training of patients and their carers in the correct use of the product is important and manufacturers were required to update their educational materials
• manufacturers should carry out studies in humans to more fully understand when and how much adrenaline reaches the blood stream, and how quickly and effectively it acts on body tissues when given through an auto-injector

EAACI guideline says number of pens should be guided by individual assessment, and BSACI also allow that 2 pens may be more appropriate in some cases, eg obesity, previous need for 2 doses, remoteness etc. There has been good evidence published indicating that one-third of children with anaphylaxis require a second dose of epinephrine (Kornblat P, et al Allergy Asthma Proc. 1999; 20: 383–6), and deaths have occurred despite a single injection, but most of these reports describe subcutaneous adrenaline use, rather than intramuscular use. Dose is more likely to be an issue with big teenagers (eg over 45kg).

If you carry your pen, know how and when to use it, then you are doing to do significantly better if you have a bad reaction than most other people, so don’t get too hung up on how many pens!

Spare pens in school

New legislation (2017) allows schools to obtain without prescription spare pens.  These can be used if the pupil’s own pen is not immediately available or already given.  Note that children with food allergies are not always prescribed adrenaline auto injectors but may still be at risk of anaphylaxis.  The spare pen can be used in such children if:

• The child’s care plan confirms child is at risk of anaphylaxis
• A health care professional has authorised use of the spare pen in an emergency
• The child’s parent/guardian has provided consent for a spare pen to be administered

Note that advice on using pens can be given over the phone by emergency services, if it is made clear pens are available.

Further information about spare adrenaline pens, and advice on reducing the risk of reaction sin school, treating reactions in school, staff training etc can be found at https://www.sparepensinschools.uk/

Needle length

Doing ultrasounds of thighs shows that in a significant proportion of people, including children under 5 with high BMI, the distance to muscle is more than 15mm (and not including any clothing). 82% of the obese children studied had skin surface to muscle depth greater than needle length. This was only true for 25% of the non-obese children. 3/4 the way down the thigh, only 17% of obese children and 2% of those not obese. Arkwright, Royal Manchester Children’s Hospital –  2013 Annual AAAAI meeting.

Some suggestion from injection models that “jet” of adrenaline penetrates significantly deeper than needle alone, that the angle, force used, whether the device is spring loaded or not, all potentially affect depth. So concerning, especially given the cases where multiple injections have failed to prevent death (eg Natasha Ednan-Laperouse).

Emerade had longer needle (25mm) but not currently available.  So inject in lower lateral thigh?

2015 European medicine agency review discussed above concluded that training remains the paramount issue, although further research into needle length should be done.

2021 Review found that blood adrenaline levels actually higher after Epipen and Jext cf

Failure to use

In a 3 year Canadian study of 1500 ED episodes, almost 50% of adults were not treated with epinephrine in or outside of the hospital.  Slightly better for kids, 28.7%.  Almost all of these children had been prescribed auto-injectors.  The need for multiple doses in ED was less in those who received epinephrine outside ED.  [Allergy, Asthma & Clinical Immunology 2014, 10(Suppl 2):A3  doi:10.1186/1710-1492-10-S2-A3]

In a Canadian email survey of 1885 anaphylaxis survivors (adults and kids, food and insect etc), 73% did not give epipen.  Most common reason for not giving, was that an antihistamine had been given first.  Only 28% gave reason as being that they did not have epipen! 13% judged reaction as mild.  41% of epipens were given by someone other than patient, mostly family of children.  53% of epipen users had previously used one before.  [simons, clark, camargo – JACI 2009:124;301 doi:10.1016/j.jaci.2009.03.050]

Failure to prescribe

In an online survey presenting 10 paediatric allergy case histories to paediatricians (all were severe, although only 1 case specifically mentioned anaphylaxis).  There was significant variability in prescribing practices. Although all allergists and generalists prescribed an autoinjector (94.4% and 92.6%, respectively) or would offer the patient a choice about autoinjectors (5.6% and 7.4%, respectively) in the case specifically mentioning anaphylaxis, many cases had almost no consensus on prescription of adrenaline autoinjector. The prescribing patterns of allergists and generalists showed no significant differences for 9 of the cases. For the remaining case, which described a child with oral allergy syndrome, all specialists (n=54, 100%) reported that they would not prescribe an autoinjector (in line with guidelines) compared with only 20 (74.1%) of generalists (p<0.001).  [Johnson MJ, Foote KD, Moyses HE et al. (2012) Practices in the prescription of adrenaline autoinjectors. Pediatric Allergy and Immunology 23: 124-7]

In a survey of all GPs in Scotland, 90% of the 613 respondents had prescribed adrenaline autoinjectors. However, only 49% of prescribers were confident in use of these devices, and only 17% had access to a trainer pen for demonstration to patients. If called upon in an anaphylactic emergency (experienced by 36% of respondents), only 50% of respondents would use the appropriate dose and 14% would use an inappropriate route of administration (subcutaneous or intravenous).  [Lowe G, Kirkwood E, Harkness S (2010) Survey of anaphylaxis management by general practitioners in Scotland. Scottish Medical Journal 55:11-4]

Failure to Use – Doctors

When scenarios presented to junior doctors (same questions posed 10 years earlier) – all recognized need for adrenaline in anaphylaxis scenario but dose often wrong and 25% gave adrenaline IV.  For non-anaphylactic scenarios, adrenaline frequently recommended eg inhaled peanut.  Not much improvement over decade.  [Postgrad Med J 2015;91:3-7 doi:10.1136/postgradmedj-2013-132181 ]

Editorial discusses how doctors know that adrenaline is required in anaphylaxis, but that this knowledge is often not translated into practice. Many of these doctors had had ALS training; most had not worked in an emergency department.  Simulation?  Australian experience.  Booster sessions?

Accidental self-injection

See accidental adrenaline self-injection.