According to the World Allergy Organization's anaphylaxis guidance, anaphylaxis can be defined as:
‘A serious multi-systemic hypersensitivity reaction that is usually rapid in onset and may result in death.’
Turner et al (2019) stated that severe anaphylaxis is characterised by a potentially life-threatening compromise of the airway, breathing and/or the circulation, and may occur without typical skin features or circulatory shock being present. Anaphylactic reactions can be fatal within minutes. It is therefore essential that health professionals recognise the signs and symptoms of a reaction and implement the correct treatment immediately (Resuscitation Council UK (RCUK), 2021).
The aim of this article is to discuss the immediate emergency management and post-emergency management of an adult patient experiencing an anaphylactic reaction.
Epidemiology of anaphylaxis
Prevalence and incidence
Anaphylactic episodes are increasing within the UK, with growing numbers of people presenting to hospitals. Between 2018 and 2019, data revealed that there were 3864 hospital admissions due to anaphylactic shock in adult patients, an increase on 3337 hospital admissions in 2015 to 2016 (NHS Digital, 2021) Overall, both adult and child admissions were 4482 in 2015-2016 and 5534 in 2018-2019).
Yu and Lin (2018) carried out a review of studies on anaphylaxis and found an estimated lifetime prevalence of 0.05% in the USA and 3% in Europe. According to Yu and Lin's review (2018), several studies have suggested that there has been an increase in emergency admissions to hospital for patients experiencing anaphylaxis, both in the USA and Europe. There appears to be much variation in anaphylaxis statistics. A systematic review by the European Academy of Allergy and Clinical Immunology's Food Allergy and Anaphylaxis Group estimated the incidence rate for all-cause anaphylaxis to be 1.5 to 7.9 per 100 000 of the European population (Panesar et al, 2013). The data also indicated that an estimated 1 in 300 people in Europe are at risk of experiencing an anaphylactic reaction during their lifetime (Panesar et al, 2013). These figures are lower than those reported in the USA, but this may be because of differences in criteria used when diagnosing anaphylaxis in each area (RCUK, 2021).
Baseggio Conrado et al (2021a) also carried out a systematic review of the data and, regarding food-related anaphylaxis, found that European populations had a higher prevalence of this type of anaphylaxis, with crustaceans and cow's milk being the predominant causes. This compared with south Asian populations, where the main causes of food-related anaphylaxis were fish and crustaceans. Any food or substance in any geographical location could potentially cause anaphylaxis. This is why potential food allergens must be labelled on foods worldwide, depending on the demographics of their population. Baseggio Conrado et al's (2021a) review of the data also showed that children in Europe and Asia had an increased risk of anaphylaxis compared with adults.
Mortality
The overall prognosis for anaphylaxis is good in the UK when prompt presentation to hospital and recognition of the condition occur (Turner et al, 2015). Statistically, approximately one person per million dies annually from an anaphylactic reaction to food, venom or medication-induced anaphylaxis in the UK (Turner et al, 2017). The risk of death increases if a patient has comorbidities such as asthma. It has also been stated that health professionals who have not had much exposure to patients experiencing an anaphylactic reaction might mistake it for an asthma attack. This can delay the use of adrenaline, which is linked to poorer patient outcomes (Pumphrey and Gowland, 2007).
Triggers
Any food or medication can cause anaphylaxis. According to Baseggio Conrado et al (2021b) and the RCUK (2021) the most common food triggers of anaphylaxis, of all severities, accounting for 35% of hospital admissions, are:
- Peanuts
- Tree nuts
- Cow's milk (in children).
However, one-third of reactions are described as idiopathic, where a trigger cannot be determined, or another immunological response is the causation (Turner et al, 2015). Teenagers and young adults up to the age of 30 years are most at risk from death due to anaphylaxis, but a fatal reaction due to medication is an increased risk for elderly patients (Turner et al, 2015; Baseggio Conrado et al, 2021b). This has been attributed to greater comorbidities involving cardiac function and polypharmacy, which is known to affect this population. The use of angiotension-converting enzyme (ACE) inhibitors, for example, can be detrimental to someone experiencing an anaphylactic reaction (Tejedor-Alonso et al, 2019).
The most common medication triggers are antibiotics and chemotherapy drugs, which account for 17% of hospital admissions for anaphylaxis and 39% of anaphylaxis-related deaths (Pumphrey, 2004; Turner et al, 2015; Harper et al, 2018; RCUK, 2021: 16).
Insect stings account for 6.5% of admissions for anaphylaxis and 14% of anaphylaxis-related deaths (Turner et al, 2015; RCUK, 2021: 16).
Pathophysiology
Anaphylaxis is a type 1 hypersensitivity (an immunoglobulin E (IgE)–mediated mast cell degranulation reaction) (Delves et al, 2017). This reaction is categorised by constriction of the bronchioles and bronchi, contraction of smooth muscle and dilatation of the capillaries with multi-systemic involvement (Delves et al, 2017).
In anaphylaxis the immune system reacts to antigens (allergens) to which the body has been exposed and mounts an immune response. These antigens can be anything from food substances to medications and bee venom (Helbert, 2017). The antigen helps to generate a specific antibody called an IgE where the allergen binds to the site (Abbas et al, 2018).
The first cells within this process are antigen-presenting cells that absorb the allergen and then present it on the cell surface receptors and communicate the findings to the immune system. T-helper cells are then dispatched, which have been through a strenuous maturation process enabling them to respond to the allergen. The T-helper cells then bind with the antigen-presenting cells (Nadeau et al, 2012).
The T-helper cells then communicate with the immune system, stating there is a problem, and triggering the involvement of B-cells (Galli and Tsai, 2010). The B-cells then attach the allergens to their cell surface receptors and starts making IgA and IgB but not IgE (Mangan et al, 2004).
The T-cells then communicate with the B-cells through a chemical messenger called a cytokine and tell them to switch to making IgE. These IgE antibodies are then released and attach to immune cells called mast and basophils cells through cross-linking. These cells both produce an inflammatory agent called histamine. It is also important to note that, through degranulation, there can be an immediate release of histamine stored within the mast and basophil cells, therefore creating the physiological effects of anaphylaxis (Kraft and Kinet, 2007).
Management of anaphylaxis
Recognition
Anaphylaxis is likely if a patient is exposed to an allergen (trigger) to which they are known to be allergic. They may then suddenly deteriorate rapidly, usually within minutes, or, in some instances, a delayed reaction can manifest. These usually rapidly developing symptoms can consist of rapidly progressing skin changes and usually airway/breathing or circulatory problems (RCUK, 2021: 20). The reaction is often unexpected, and the patient will have a sense of impending doom, such as feeling as if they are dying (Australasian Society of Clinical Immunology and Allergy (ASCIA), 2020).
Anaphylaxis is likely when all three of the following criteria are met (RCUK, 2021: 21):
- Sudden onset and rapid progression of symptoms
- Life-threatening airway and/or breathing and/or circulation problems.
- Skin and/or mucosal changes (flushing, urticaria, angioedema).
The following evidence will support the diagnosis (past medical history):
- Patient exposure to a known allergen, for example a known antibiotic or food substance.
It is crucial to consider:
- Skin or mucosal changes alone are not a sign of anaphylaxis and can be absent in 20% of patients (some may present only with hypotension)
- Gastrointestinal symptoms have also been noted (such as vomiting/nausea, abdominal pain and diarrhoea).
The RCUK (2021: 23) states that, to distinguish between a vasovagal episode and anaphylaxis, an ABCDE approach can be taken, although a patient may not have all the following features:
- A. Airway problems
- Airway swelling, including throat and tongue (pharyngeal/laryngeal oedema)
- Hoarse voice
- Stridor.
- B. Breathing problems
- Wheeze
- Shortness of breath
- Hypoxia resulting in confusion
- Cyanosis
- Respiratory arrest
- Exacerbation of life-threatening asthma.
- C. Circulatory problems
- Signs of shock
- Tachycardia
- Hypotension
- Decreased Glasgow Coma Scale score
- Myocardial ischaemia
- Cardiac arrest.
- D. Disability
- Decreased neurological status
- Central nervous system effects
- Confusion
- Agitation
- Loss of consciousness
- Anxiety
- Gastrointestinal symptoms: abdominal pain, vomiting, incontinence.
- E. Exposure (skin)
- Patchy erythema or generalised rash
- Skin and mucosal membrane changes
- Urticaria
- Angioedema of deeper tissues: eyelids, lips, tongue, throat.
Initial treatment
Initial treatment will vary depending on the setting and skills and equipment available at the time. Initial treatment should always consist of stopping an infusion of antibiotics or other medication, if this is thought to be the cause, and administering 1:1000 intramuscular (IM) adrenaline as soon as possible. This will reduce airway swelling and increase blood pressure. Then the ABCDE approach should be implemented and treatment commenced throughout the protocol as it arises (RCUK, 2021: 23). When available, full monitoring should be applied, including pulse oximetry, non-invasive blood pressure and a minimum of a 3-lead ECG (ASCIA, 2020).
Patients with breathing problems should sit up. If a patient has low blood pressure and breathing is not compromised, the patient should lie flat with their legs elevated to help increase blood pressure. Allowing the patient to stand may lead to a cardiac arrest. If a patient does go into cardiac arrest cardiopulmonary resuscitation should be performed immediately (Lott et al, 2021).
First-line drug treatment
Only a limited number of drugs are used in the treatment of anaphylaxis. The most important being 1:1000 adrenaline (epinephrine) as evidence shows the prompt administration of this drug in the early stages of an anaphylactic reaction correlates with a better clinical outcome (Sheikh et al, 2009).
Drugs used initially according to the RCUK (2021) are:
- 1:1000 IM adrenaline (repeat after 5 minutes if no change)
- 1:1000 intravenous (IV) adrenaline (used only by experienced specialists in a critical care setting)
- Nebulised adrenaline for upper respiratory oedema (after IM/IV adrenaline)
- High-flow oxygen (give as soon as available)
- IV fluids (hypotension and severe anaphylaxis): establish IV access then give 500-1000 ml in an adult using initially non-glucose-containing crystalloids such as Hartmann's. If further fluid doses are needed a non-glucose-containing crystalloid should be used. If needed, the intraosseous (IO) route can be used.
Antihistamines and steroids are not recommended in the initial treatment of anaphylaxis.
Second-line drug treatments
Antihistamine use (H1-antihistamine) is recommended as a second-line treatment for anaphylaxis even though the evidence is weak. Corticosteroids such as hydrocortisone can help shorten reactions and prevent reoccurrence (RCUK, 2021).
Investigations
Acute clinical features of presentation—rapid onset, ABCDE involvement and so on, should be documented (RCUK, 2021):
- Record the time of onset
- Record circumstances immediately before symptoms (this may help to identify trigger)
- Take a time-recorded blood sample for a mast cell tryptase test after emergency treatment, then another 1-2 hours after the first but no later than 4 hours. On referral to a specialist allergy clinic, this test may need to be repeated
- Observe the adult patient for at least 6-12 hours from onset of symptoms
- Discharge and follow up.
Discharge should only be initiated after a senior clinician has reviewed the patient. All patients should be offered education on anaphylaxis by trained and competent staff, including what to do in an emergency and how to use an adrenaline (epinephrine) auto-injector (EpiPen).
Patients should be offered a referral to an allergy clinic for follow up, using each hospital's individual referral pathway. The RCUK (2021) recommends following National Institute for Health and Care Excellence guidance (2020) for the assessment and referral of patients.
Conclusion
In the UK, anaphylactic reactions are increasing. The RCUK (2021) emergency guidelines for treating patients experiencing a suspected anaphylactic reaction have been updated recently. The emphasis is on prompt recognition, administration of adrenaline and the ABCDE approach. Treatment depends on the location of the patient and the equipment/skills available. All patients should be referred to an allergist immediately after experiencing an anaphylactic reaction.
KEY POINTS
- Anaphylaxis is a serious multi-systemic hypersensitivity reaction that is usually rapid in onset and may result in death
- Anaphylaxis is characterised by a potentially life-threatening compromise of the airway, breathing and/or the circulation
- Anaphylaxis may occur without typical skin features or circulatory shock being present
- Anaphylactic reactions can be fatal within minutes, without prompt recognition and treatment, ie administration of (intramuscular) adrenaline (1:1000)
CPD reflective questions
- What can you do to increase awareness within the multidisciplinary team of the dangers of an anaphylactic reaction?
- What can you do to improve awareness of the key presenting signs and symptoms of a patient suffering an anaphylactic reaction?
- Do you and your colleagues know the treatment needed for an anaphylactic reaction, including medication, that needs to be administered during a reaction?
- Considering the several themes within this article, which can you identify and reflect upon, with the wider multidisciplinary team?