Guidelines

Adrenaline is the first-line treatment for anaphylaxis and is recommended in the major guidelines including the British Society for Allergy and Clinical Immunology (BSACI), Resuscitation Council UK and the European Academy of Allergy and Clinical Immunology (EAACI).^1-3

BSACI Guidelines on prescribing an adrenaline auto-injector¹

Adrenaline is the first-line treatment for anaphylaxis. It should be used in patients with significant airway involvement or hypotension, occurring as part of an anaphylactic (IgE- or non IgE-mediated) reaction. An auto-injector allows early administration of adrenaline therefore improving patient outcomes.¹

BSACI Guidelines

Resuscitation Council UK - Emergency treatment of anaphylactic reactions: Guidelines for healthcare providers²

Treatment of anaphylaxis should be based on general life-support principles:

• Call for help early
• Use the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach to recognise and treat problems. Treat the greatest threat to life first
• Give IM adrenaline to treat Airway/Breathing/Circulation problems
• Initial treatment should not be delayed by a lack of a complete history or definite diagnosis
• Repeat IM adrenaline after 5 minutes if features of anaphylaxis do not resolve

Standard practice for healthcare professionals, particularly in the hospital is to use a vial of adrenaline, syringe and needle.²

Adrenaline (give IM unless experienced with IV adrenaline)

IM doses of 1:1000 adrenaline (repeat after 5 min if no better)²

• Adult 500 micrograms IM (0.5 mL)
• Child more than 12 years: 500 micrograms IM (0.5 mL)
• Child 6 -12 years: 300 micrograms IM (0.3 mL)
• Child less than 6 years: 150 micrograms IM (0.15 mL)

The scientific evidence for the recommended doses is weak. The recommended doses are based on what is considered safe and practical to draw up and inject in an emergency. In all healthcare settings, giving adrenaline from an ampoule by syringe and needle is preferred in an emergency.²

Resus Guidelines

The EAACI task force recommends promptly using intramuscular adrenaline in the mid-thigh area as first-line management of anaphylaxis.

The EAACI task force suggests prescribing 0.15 mg adrenaline auto-injectors for children from 7.5 kg to 25-30 kg and 0.3mg adrenaline auto-injectors for children from 25-30 kg and at least 0.3 mg adrenaline auto-injectors for adolescents and adults at risk of anaphylaxis.

The EAACI task force recommends providing structured and comprehensive training to improve knowledge and use of adrenaline auto-injectors in people at risk of anaphylaxis. This is in addition to basic instructions about auto-injector use.

EAACI Guidelines

MHRA Advice

In addition, the MHRA have published drug safety update advice on adrenaline auto-injectors.

• It is recommended that 2 adrenaline auto-injectors are prescribed, which patients should carry at all times
• Ensure that people with allergies and their carers have been trained to use the particular auto-injector that they have been prescribed - technique varies between injectors
• Encourage people with allergies and their carers to obtain and practice using a trainer device (available for free from the manufacturers’ websites)

MHRA advice to give to people with allergies and their carers⁴

• It is recommended that you carry 2 adrenaline auto-injectors at all times; this is particularly important for people who also have allergic asthma because they are at an increased risk of a severe anaphylactic reaction
• Use the adrenaline auto-injector at the first signs of a severe allergic reaction
• Take the following actions immediately after every use of an adrenaline auto-injector:
1. Call 999, ask for an ambulance and state “anaphylaxis” even if symptoms are improving
2. Lie flat with legs raised to maintain blood flow. However, if you have breathing difficulties, you may need to sit up to make breathing easier
3. Seek help immediately after using the auto-injector and if at all possible make sure someone stays with you while waiting for the ambulance
4. If you do not start to feel better, use the second auto-injector 5-15 minutes after the first one
• Check the expiry date of the adrenaline auto-injectors and obtain replacements before they expire; expired injectors will be less effective

MHRA Advice

In 2021, recommendations to support the effective and safe use of adrenaline auto-injectors were produced via a public assessment report of the commission on human medicines’ adrenaline auto-injector expert working group (EGW).⁵

The AAI EWG made a range of recommendations that can be summarised as follows:⁵

• An AAI should be administered early, at the first signs of anaphylaxis, given clear evidence that this improves patient outcomes
• The patient should stay lying down, with legs elevated where possible, to assist blood flow back to the heart and to vital organs. If patients are struggling to breathe, they may need to sit up but this should be for as short a time as possible. It is imperative to avoid any sudden change in posture and above all, the patient must not be allowed to stand up, or sit in a chair, even if they are feeling better
• Patients at risk of anaphylaxis should have two AAIs available to them at all times. This is to meet the potential need for a second dose of adrenaline before the arrival of the emergency services, which is not uncommon
• Trainer devices are available from all the manufacturers, on request. Patients and carers are strongly encouraged to obtain these to ensure familiarity with the particular brand supplied as there are important differences in the way each is used
• The strength of an AAI reflects the amount of adrenaline administered per injection but this does not necessarily reflect the amount of adrenaline that reaches the bloodstream (the “bioavailability”), particularly in the early time period following injection which is the most critical period for the patient. Adrenaline bioavailability (levels in the blood) may be influenced not only by the administered dose but also by factors specific to the device and the patient. For example, the amount of adrenaline reaching the bloodstream in the early period may be affected by device-specific factors such as the length of the needle which will affect the depth of penetration of the adrenaline, as well as the force of injection
• Pharmacokinetic (adrenaline blood level) data are now available for all marketed devices in the UK. The data are included in summary form in section 5.2 of the SmPC for all devices. Adrenaline levels in the bloodstream were demonstrated to be overall higher, as a proportion of dose administered, in the first 30 minutes following injection with the higher strength presentations of devices with shorter needles, compared with the device which has a longer needle. This suggests that needle length may not be the predominant factor affecting adrenaline uptake into the bloodstream and that the force of injection may also be important
• Although some AAIs are available in a maximum strength of 300 mcg, these AAIs deliver more adrenaline, as a proportion of dose, to the bloodstream in the first 30 minutes following injection, compared with 500 mcg.

1. Ewan P et al. BSACI guideline: prescribing an adrenaline auto-injector. Clinical & Experimental Allergy, 46, 1258-1280
2. Resuscitation Council UK Anaphylaxis Guidelines. Available at: https://www.resus.org.uk/sites/default/files/2021-05/Emergency%20Treatment%20of%20Anaphylaxis%20May%202021_0.pdf. Last accessed: May 2023
3. Muraro A, et al. EAACI guidelines: Anaphylaxis. 2022;77: 357-377
4. MHRA Advice. Available at: https://www.gov.uk/drug-safety-update/adrenaline-auto-injectors-updated-advice-after-european-review. Last accessed: May 2023
5. Public Assessment Report of the Commission on Human Medicines’ Adrenaline Auto-injector Expert Working Group: Recommendations to support the effective and safe use of adrenaline auto-injectors. Available at: https://www.gov.uk/government/publications/public-assessment-report-recommendations-to-support-the-effective-and-safe-use-of-adrenaline-auto-injectors/public-assessment-report-of-the-commission-on-human-medicines-adrenaline-auto-injector-expert-working-group-recommendations-to-support-the-effectiv. Last accessed: May 2023