Anaphylaxis - a race against time

Adrenaline is the first line emergency treatment for anaphylaxis and failure to inject it in a timely manner can be fatal.1 With over 575,000 EpiPen® auto-injectors expiring this year,2 doctors, nurses and pharmacists are urged to help remind their patients of the need to always 'check & carry' their device.

Anaphylaxis is a rapid-onset, serious allergic reaction.3 Minute quantities of an allergen trigger the release of mast cell mediators such as histamine, leukotrienes and cytokines. This reaction may lead to life-threatening symptoms of bronchospasm, upper airway obstruction and sometimes hypotension. The multi-organ involvement of these mediators means that a medical response is required to rapidly resolve the symptoms and avoid a potentially fatal outcome.

Epidemiology
Anaphylaxis is estimated to affect between 30 and 950 per 100,000 population or approximately one in 3,500 people in the UK population.4 The outcome of severe anaphylaxis is fatal in 0.65-2% of cases5 and risk is increased in individuals with poorly-controlled asthma or in those with asthma where treatment with adrenaline is delayed.4 Previous exposure to a severe anaphylactic reaction and being aged over 35 also increases the risk of a fatal outcome.6

Symptoms and causes
Symptoms of an anaphylactic reaction can be wide-ranging, inconsistent and may include the following:

  • tingling and swelling of the lips, eyes or face
  • itching or rash (urticaria)
  • tightening of the throat (angioedema)
  • tachycardia
  • difficulty breathing (bronchospasm)
  • hypotension
  • sense of impending doom

Onset of symptoms is usually very rapid and a patient may develop severe breathing difficulties or hypotension within minutes of exposure to the trigger. The severity of the symptoms is less predictable. In some cases, a mild reaction can be followed by a later and more severe secondary (biphasic) reaction, occurring any time between one to 72 hours after treatment. These secondary reactions can be mild and resolve without further therapy or be potentially fatal.7  The Resuscitation Council recommends that all patients experiencing life-threatening airway and/or breathing and/or circulation problems are observed for at least six hours following resolution of initial symptoms.

The most common triggers of anaphylaxis are food, insect venom (for example, wasp or bee stings) and medications.6  Common food triggers include peanuts, tree nuts (for example, almonds, walnuts, cashews), seeds, seafood, dairy products and eggs.6 The most common medical triggers of anaphylaxis are antibiotics (particularly, penicillin's and cephalosporin's), muscle relaxants, NSAIDS and aspirin.4

 

Assessing the risk - the link with asthma
The risk of anaphylaxis within a population with no diagnosed prior allergy or previous anaphylactic reaction is almost impossible to predict.3 However, asthma has a significant influence on the likelihood of anaphylaxis and the possibility of a fatal outcome as well the severity of recurring anaphylaxis.8 Asthma is found in 33% of children with food allergy.9 A population-based incidence study spanning 10 years,3 found that 59% of patients admitted with clinically-confirmed anaphylaxis had a medical history of allergy problems, and approximately half of those patients had asthma.

One in 12 patients who have suffered anaphylaxis will experience a recurrence10 and the severity of subsequent reactions is unpredictable. The Resuscitation Council recommends that all patients at continued high risk of reaction, for example, those experiencing venom or food-induced reactions are provided with emergency treatment in the form of self-administered adrenaline and referred to an allergy clinic for further assessment and provision of a detailed management plan tailored to their specific case.

Treating anaphylaxis: importance of adrenaline
Adrenaline is the drug of choice for first-line treatment of anaphylaxis. It is administered by intramuscular injection (IM) in the anterolateral aspect of the thigh and works quickly to reverse the symptoms of an anaphylactic reaction.

The varied and unpredictable course of severe allergic reactions makes it difficult to define the most appropriate timing for administration of adrenaline. However, early use of intramuscular adrenaline is associated with improved outcomes11 as well as the potential reduction in the need for a second dose.12 Adrenaline should be given to all patients with life-threatening features, for example evidence of breathing difficulties and hypotension.4

In one in three patients a single dose of adrenaline is not sufficient to completely reverse the effects of anaphylaxis.13,14,15 In the absence of clinical improvement or if there is deterioration following initial treatment a second dose of adrenaline may be required after a 5-15 minute interval.16 There are two different devices available to deliver intramuscular adrenaline known as Adrenaline Auto-injectors or AAIs, Anapen® or the more commonly used EpiPen®. The two devices work quite differently and are not interchangeable.

EpiPen® Auto-Injector
EpiPen® Auto-Injectors are a disposable, automated drug delivery system featuring a spring-loaded concealed needle. It is designed for rapid self-administration of a single dose of adrenaline in individuals experiencing potentially life-threatening anaphylaxis. EpiPen delivers a 0.3mg dose and EpiPen Junior delivers a 0.15mg dose.

Using EpiPen®Auto-Injector
Correct administration of adrenaline using an EpiPen is extremely important in order to avoid intravenous injection. The auto-injector should only be injected into the anterolateral aspect of the thigh and not in the buttock. Directions for correct use of an EpiPen are summarised below and in a video on the site.

A race against time
In fatal anaphylactic reactions, death can occur within 15 minutes following exposure to venom and within 30 to 35 minutes of exposure to food.17,11 Therefore, rapid achievement of maximum concentrations of adrenaline is extremely important. Intramuscular (IM) injection of adrenaline with EpiPen Auto-Injector results in achievement of peak plasma adrenaline concentration (Tmax) within eight minutes and within the median time to arrest following exposure to venom or food allergen as shown below.

Carrying an up-to-date adrenaline auto-injector (AAI)
Thirty-two percent of patients prescribed an adrenaline auto-injector fail to replace their pen(s) within 18 months which means that almost one in three patients may be carrying an expired auto-injector.18 Due to manufacturing cycles a significant proportion of EpiPen's tend to expire within a short time-frame.  Patients should be advised to check the expiry date indicated on the label of their AAI at regular intervals and replace it by that date.

The EpiPen Expiry Alert Service
A convenient way of ensuring that patients replace their EpiPen prior to the expiry date is to register with the EpiPen Expiry Alert Service provided free by the manufacturer ALK-Abelló. This can be accessed through their website at www.alk-lifeline.co.uk or alternatively patients can register via SMS text message by texting Alert followed by the month and year their EpiPen expires to 80818. Once registered, a reminder is sent by SMS text message and/ or e-mail depending on the patient's preference.

Resources
Patients may be advised about The Anaphylaxis Campaign, a UK based charity dedicated to providing support and advice to people affected by life-threatening allergy. Their website can be found at www.anaphylaxis.org.uk. Further information about allergy, anaphylaxis and their management can be found on the following websites:

Specific information about EpiPen and anaphylaxis can be found at www.alk-lifeline.co.uk

Click here for Prescribing Information

References

  1. Simons E et al. J Allergy Clin Immunol 2009; 301-306
  2. Data on file. ALK-Abéllo 2010
  3. Decker WW, Campbell RL, Mannivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project. J Allergy Clin Immunol 2008;122(6):1161-1165.
  4. The Resuscitation Council (UK). Emergency treatment of anaphylactic reactions: Guidelines for healthcare providers 2008.
  5. Muraro A et al. Allergy 2007;62:857-871.
  6. Brown SGA, Mullins RJ, Gold MS. MJA Practice Essentials - Allergy. 2. Anaphylaxis diagnosis and management. MJA 2006;185(5):283-289.
  7. The Anaphylaxis Campaign website, viewed 18.05.2010
  8. Pumphrey RSH. Clin Exp Allergy 2000;30:144-50.
  9. Roberts G et al . JACI 2003;112:168-74.
  10. Mullins RJ. Anaphylaxis: risk factors for recurrence. Clin Exp Allergy 2003;22:1033-40.
  11. Pumphrey RSH. Clin Exp Allergy 2000;30:144-50.
  12. Kelso JM. A second dose of epinephrine. How often needed and how to carry. J Allergy Clin Immunol 2006;117(2):464-52006.
  13. Korenblat P et al. Allergy Asthma Proc 1999;20:383-6.
  14. Webb L et al. J Clin Immunol 2004;13(suppl 1):S240. Abstract 857
  15. Varghese M and Lieberman P. Abstract presented at AAAAI Annual Meeting 2006. Miami, USA.
  16. EpiPen Summary of Product Characteristics and Resuscitation Guidelines
  17. Simons FER, Roberts JR, Gu X, Simons KJ. J Allergy Clin Immunol 1998;01:33-7.
  18. Lombardelli & Edgar, Poster presented at British Society of Allergy & Clinical ImmunologyJuly 2009.

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