Confirmed or suspected anaphylaxis should always be treated as a medical emergency as cardio-respiratory collapse can be fatal if not managed urgently.

The emergency management of anaphylaxis is fully described within the UK Resuscitation Council Guidelines and is summarised in their associated algorithm. An adapted version of this algorithm is available to download here.

Patient Assessment

Patients with a suspected anaphylactic reaction should be assessed using the ABC algorithm to identify life threatening symptoms of anaphylaxis.

Life threatening symptoms include:

• Airway: swelling, hoarseness, stridor
• Breathing: rapid breathing, wheeze, cyanosis, fatigue
• Circulation: pallor, clammy, hypotension, faintness

Confirmed or suspected anaphylaxis is a medical emergency and can be fatal if not managed appropriately.

An ambulance should always be called and “anaphylaxis” stated.

Intramuscular adrenaline

The treatment of choice for anaphylaxis is intramuscular adrenaline which should be administered into the anterolateral aspect, or outer side, of the middle third of the thigh.

There are no absolute contra-indications to the use of adrenaline in the management of anaphylaxis.

The intra-muscular route is advised because it provides quicker adrenaline absorption when compared to the subcutaneous route. The rate of absorption of adrenaline is higher when administered into the thigh in comparison to administration into the arm.

Rapid absorption of the adrenaline is obviously important when considering the potentially fatal nature of an anaphylactic reaction.

Additional benefits of the intra-muscular route include:

• Increased safety margin.
• Intravenous access is not required.
• Easier administration route to learn.

Recommended dose of adrenaline

The UK Resuscitation Guidelines advise the following doses when administering adrenaline using an auto-injector:

Most patients require only a single dose but if symptoms do not improve or they recur, the dose can be repeated after five minutes. Each patient will respond differently to adrenaline, this necessitates patient responses to be monitored and additional adrenaline dose to be administered where appropriate.

After administering adrenaline the patient should be positioned as advised below and monitored.

The most appropriate position for each patient will be determined by their key presenting symptoms:

• Patients who have airway or breathing problems may be more comfortable to sit up as this makes breathing easier.
• Patients with low blood pressure should lie flat with or without their legs elevated.
• Patients who are unconscious but breathing should be placed in the recovery position.

Patients who are unresponsive and not breathing normally should be treated with cardiopulmonary resuscitation (CPR) immediately. Before starting CPR it is essential to ensure an ambulance has been called and medical support is on the way.

Following administration of adrenaline patients should be admitted to hospital and observed for at least six hours. Where the patient responds well to treatment, they should be warned of the possibility of a relapse in their symptoms; the biphasic reaction as discussed in the module Anaphylaxis- Clinical Symptoms.[CH2] 

In certain circumstances the patient will be monitored for up to 24 hours. This would include:

• Severe reactions associated with a slow onset with an unknown trigger.
• Patients with severe asthma.
• Reactions where ongoing absorption of the allergen is possible.
• Previous history of biphasic reactions.
• Evening or night time presentation where there may be reduced response to deterioration.
• Areas where there is difficult or limited access to emergency care.

Mechanism of action of adrenaline

Adrenaline is a hormone naturally produced in response to exertion or stress by the adrenal gland. Normal endogenous plasma concentrations are within the range of 30- 160ng/l.

Oral administration of adrenaline results in rapid destruction by the gastro-intestinal enzymes; adrenaline is consequently administered by injection.

Adrenaline acts at both α and β adrenergic receptors to counter the physiological effects of anaphylaxis.

Stimulation of α adrenergic receptors results in vasoconstriction which raises the blood pressure and reduces erythema, urticaria, and angioedema. It is also possible that the vasoconstrictive effect of adrenaline minimises further absorption of the allergen from a sting or injection, although this effect cannot be confirmed.

Stimulation of β adrenergic receptors causes bronchodilation alleviating bronchospasm, wheezing and breathlessness. The β stimulation also increases myocardial output and contractility, further increasing blood pressure. The β stimulant effect also suppresses further mediator release from mast cells and basophils, helping to halt the reaction.

 Cautions, contraindications and possible side effects of adrenaline

Despite concerns regarding administration of adrenaline to patients with co-existing medical conditions it is important to remember that adrenaline is used to treat a potentially life threatening allergic reaction and these concerns should not prevent prompt treatment.

Patients with these co-existing conditions will require closer observation following administration of adrenaline.

Contra-indications – there are no absolute contra-indications to the use of adrenaline in the treatment of anaphylaxis.

Cautions - adrenaline should not be administered into the gluteus maximus muscle because of the risk of administration into a vein.

Adrenaline should be used with caution in patients with existing heart disease including angina, cardiac arrhythmia, cor pulmonale, obstructive cardiomyopathy or atherosclerosis.

Adverse reactions are also possible when adrenaline is administered to patients with hyperthyroidism, hypertension, phaeochromocytoma, glaucoma, severe renal impairment, prostate adenoma, hypercalcaemia, hypokalaemia and in elderly or pregnant patients. Patients with Parkinson’s disease may notice a slight worsening of symptoms of rigidity and tremor when administered adrenaline.

Accidental injection of adrenaline into hands or feet can result in reduced blood flow to these areas and possible peripheral ischaemia.

Patients who have accidentally administered adrenaline should be referred to their local accident and emergency department

 Adrenaline Auto-Injectors (AAI)

AAIs contain a sterile solution of adrenaline either contained in a glass cartridge or pre-filled glass syringe. Jext and Epipen both comprise cartridge type AAI whilst Emerade is a syringe design.

Each AAI device has a different delivery/ administration system. All AAI contain adrenaline solution pressurised to differing degrees. This administration “under pressure” increases the force of expulsion and enables the adrenaline solution to penetrate deeper into the tissue than the length of the needle.

The currently available AAI provide a range of devices in different strengths to meet the dosage needs of different age groups. Each product will deliver the differing dose either by adjusting the concentration of the adrenaline solution contained within the glass vial or by adjusting the volume of a consistent strength adrenaline solution. This will obviously determine the volume of solution administered from each device.

The EMA has recently undertaken a review of the AAI approved in the EU. This review concluded that:

• Healthcare professionals should prescribe two AAI and patient should be advised to carry both because of uncertainties about the site of drug delivery and speed of adrenaline action.
• The product information should include details of the needle length as this is an important consideration when selecting a suitable AAI.
• Patients and carers should be trained on the correct use of the AAI supplied. The review required manufacturers to update their educational materials.
• EEA requires manufacturers to carry out studies in humans to understand when and how much adrenaline reaches the blood stream, how quickly and effectively it acts on body tissues when administered via an AAI.

Further details of the Drug Safety Update resulting from the EEA review are included in the adrenaline auto-injector medicines safety tip on NumarkNet www.numarknet.com/advice-guidance/medicines-safety-tips/adrenaline-auto-injectors-

The EEA review reinforces that there are a number of important factors to consider when selecting a brand of AAI to prescribe or supply.

Appropriate dose

The Resuscitation Council guidelines for the treatment of anaphylaxis recommend a 500mcg adrenaline dose for adults and children over the age of 12 years. Historically this has been achieved through the use of IM adrenaline 1 in 1000 (1mcg/ml) vials. A volume of 0.5mls of solution, equivalent to 500mcg, is drawn from the vial using a syringe and 23 gauge needle and injected at 90 degrees to the thigh.

Significant drawbacks to this route in a community setting are the need for additional injection technique training and the inability of patients undergoing an anaphylactic reaction to self-inject. Auto injectors overcome both these problems hence their widespread use in the community.

At the time of writing only the Emerade range has an AAI with a 500mcg dose. Jext and Epipen have a maximum strength device of 300mcg.

Needle length

This is a key consideration in the design of AAI and in prescribing decisions. There is a concern that owing to increasing rates of obesity and gender differences in thigh tissue depth, needle lengths in currently available AAI devices may not be adequate to ensure effective delivery of adrenaline into the thigh muscle.

In order for adrenaline to be effective it is important for it to be administered intramuscularly; subcutaneous administration can result in a slower rate of absorption and lower peak adrenaline plasma concentrations.

Skin to muscle depth - Gender differences and inter-patient variation in skin to muscle depth (STMD), along with an increasing prevalence of obesity, may mean that currently available AAI cannot guarantee intramuscular administration.

Females tend to have a thicker subcutaneous layer on the thigh than men and obesity results in fat deposition around the thigh increasing the STMD.

 Injecting technique - there are two key methods of self-injecting adrenaline with an AAI; either a “swing and jab” method or a “place and press” method. The method of administration is partly determined by the activation force required for the individual device. It can also result in a tissue compression effect reducing the skin to muscle distance.

Summary

Despite pressurised doses and tissue compression there remains a concern that certain patient groups may receive adrenaline subcutaneously rather than intramuscularly. This is because the length of the needle may not be long enough to penetrate the muscle fascia and allow adrenaline to reach the muscle tissue. This could result in a reduced response to treatment.

Patient groups at risk are female patients and young children. The risk in children is associated with shorter needles being used in lower dose AAI.

Where there is a possibility that patients may have a larger than average STMD it would be advisable to use an AAI with a longer needle length. Currently Emerade is the only available AAI with a needle length exceeding 20mm. For pharmacists delivering vaccination services, without the foresight of knowing the patient’s likely STMD, it would seem prudent to stock devices with longer needles.

The following table compares the key features of the individual AAI:

 

Self-help advice for patients at risk of anaphylaxis

Pharmacists are ideally positioned to advise patients, their family or carers on how to avoid an anaphylactic reaction, recognise the early symptoms of a reaction and also how to use their AAI.

Counselling could take place when supplying an AAI, during an advanced service such as an MUR or opportunistically within the pharmacy.

Suitable advice to provide would include:

• Recognise what triggers a reaction and avoid the triggers
• Where food is the identified trigger factor:
  • Be vigilant and check food labels.
  • Ask questions about what is in foods when eating out or having a takeaway.
  • Avoid food where you are unsure of the ingredients.
  • Be especially careful during festive occasions such as weddings or parties.
  • Ensure you can recognise the early symptoms of a reaction.
  • Use the AAI at the first sign of a reaction. If in doubt whether your reaction is severe use your AAI.
  • Practice using your AAI using a suitable placebo device, and encourage family and friends to practice too.
  • Ensure your family and friends can recognise the symptoms of an episode and are able to administer your AAI.
  • Ensure you always carry two AAI, this is especially important for patients with allergic asthma as they have an increased risk of severe anaphylactic reaction.
  • AAIs are designed for administration through clothing.
  • When administering an AAI try to avoid zips, buttons, buckles, seams and pocket contents.
  • Only use each device once.
  • Always call 999 and state “anaphylaxis” if you have a reaction.
  • Check the expiry dates of your AAI regularly, and obtain a replacement before they expire.
  • Register for the expiry date alert service relevant for your AAI.
  • Consider wearing a form of alert or identification device e.g. medic alert bracelet or chain that provides information on the type of anaphylactic reaction and identified triggers.

Advise patients travelling abroad to:

• Check with the airline whether the AAI can be carried on the plane.
• Carry the AAI in hand luggage.
• Take a letter from their GP as this may be required for foreign travel.
• Take travel certificates which can be downloaded from most AAI manufacturer websites.
• Take translation cards which are available from the Anaphylaxis Campaign.
• Carry the translations for specific triggers when travelling abroad and also a translation of the phrase “anaphylaxis”.
• Keep AAIs out of direct sunlight, excessive heat or light because this will cause adrenaline to turn brown.
• Make sure they know how to contact the emergency services when abroad.
• Travel with comprehensive travel insurance.

Pharmacists can also signpost patients, family members or carers to suitable patient support groups e.g. www. anaphylaxis.org.uk or resources available on AAI manufacturer websites.

Conclusion

Anaphylaxis is a potentially life threatening condition that is becoming increasingly prevalent. Pharmacists need to be able to act promptly and effectively if presented with a patient suffering an anaphylactic episode. This would require prompt recognition of symptoms and confident administration of adrenaline.

Increased provision of services such as influenza or travel vaccination will also increase the possibility of pharmacists being required to treat patients suffering anaphylaxis following vaccination.

 The selection of an appropriate device should be based on individual patient factors and the specific features of an AAI product.

 Pharmacists and technicians are ideally placed to counsel patients diagnosed with anaphylaxis and prescribed an AAI. These patients will benefit from advice on avoidance of triggers, recognition of the early signs and symptoms of anaphylaxis and training on how to self-administer adrenaline.