1. PRESCRIPTION OF SELF-INJECTABLE EPINEPHRINE Clinical Audit G.Krupa, M.Thanneermalai Paediatric Department, YDH 9/4/2008

2. Anaphylaxis Anaphylaxis is an acute, systemic, and life-threatening reaction, usually mediated by an immunologic mechanism involving immunoglobulin E, that results in sudden systemic release of mast-cell and basophile mediators such as histamine and tryptase. Anaphylaxis has many clinical presentations, but respiratory compromise and cardiovascular collapse cause the greatest concern, because they can potentially lead to fatalities.

3. Clinical Criteria for Diagnosing Anaphylaxis (Allergy Clin Immunol. 2006) Criterion 1 Acute onset of an illness (minutes to several hours) with involvement of the skin and/or mucosal tissue (eg, generalized hives, pruritus, or flushing, swollen lips/tongue/uvula) and at least 1 of the following: a. Respiratory compromise (eg, dyspnea, a. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia) expiratory flow, hypoxemia) b. Reduced blood pressure or associated symptoms of b. Reduced blood pressure or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence) syncope, incontinence)

4. Clinical Criteria for Diagnosing Anaphylaxis (Allergy Clin Immunol. 2006) Criterion 2 Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours): a. Involvement of the skin/mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula) b. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia) c. Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

5. Clinical Criteria for Diagnosing Anaphylaxis (Allergy Clin Immunol. 2006) Criterion 3 Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours) Fulfilling any 1 criterion indicates that anaphylaxis is highly likely * Mast cell serum tryptase is raised up to 5 hours following an anaphylactic reaction.

6. Clinical Criteria for Diagnosing Anaphylaxis (Allergy Clin Immunol. 2006) Additional symptoms and signs that may occur during anaphylaxis include: morbilliform rash, pruritus (skin signs aid in recognition but may be absent or not observed in 10% of children with anaphylaxis; moreover, they may not be observed in reactions that end in fatality) conjunctival erythema tightness in the throat, dysphagia, dysphonia, hoarseness, dry staccato cough, sensation of pruritus in the external auditory canals nasal pruritus, nasal congestion, rhinorrhea, sneezing chest pain, dysrhythmia, feeling of faintness/dizziness (near- syncope), paleness, cyanosis, confusion/altered mental status, an aura of doom uterine contractions

7. Role of Epinephrine Direct-acting sympathomimetic agent with effects on many target organs. Increases vasoconstriction Decreases mucosal oedema Increases inotropy/chronotropy Increases bronchodilation Downregulates further mast-cell release of histamine, tryptase, and other mediators of inflammation

8. Self-injectable Epinephrine Intramuscular injection of epinephrine into the lateral thigh (vastus lateralis) is the preferred route for therapy in first- aid treatment. Epinephrine autoinjectors are currently available in only 2 fixed doses: 0.15 mg and 0.30 mg. On the basis of current, albeit limited, data, it seems reasonable to recommend autoinjectors with 0.15 mg of epinephrine for otherwise healthy young children who weigh 10 to 25 kg and autoinjectors with 0.30 mg of epinephrine for those who weigh approximately 25 kg or more.

9. Technique for use auto-injector

10. Self-injectable Epinephrine Studies have shown that only 50-75% of patients prescribed auto-injectors for self administration of adrenaline carry them around at all times. Of these, only 30-40% were able to correctly demonstrate how they would administer adrenaline to themselves. Many others have an imperfect understanding of when to use adrenaline. When adrenaline is carried, there is a risk of excessive patient confidence, what can result in delayed arrival at hospital.

11. Indications for prescription of Self-injectable Epinephrine (Allergy Clin Immunol. 2006) Epinephrine should be prescribed for children who have experienced anaphylaxis and may re-encounter the trigger outside of a hospital setting. In some circumstances, epinephrine for self-injection should be prescribed for persons who have not experienced anaphylaxis but are at increased risk of anaphylaxis on the basis of their specific comorbid medical conditions and medical-social evaluation.

12. Examples of factors that may indicate the need to prescribe epinephrine for persons "at risk" of anaphylaxis Reaction history Reaction history Reaction to trace allergen exposure Reaction to trace allergen exposure Repeat exposures likely Repeat exposures likely Specific food triggers known to be associated with severe/fatal reactions (e.g., peanut, tree nut, seafood) Specific food triggers known to be associated with severe/fatal reactions (e.g., peanut, tree nut, seafood) Generalized urticaria from insect venom Certain comorbidities Certain comorbidities Asthma Use of nonselective β-blockers Additional factors Additional factors Initial reaction details unclear, possible anaphylaxis Initial reaction details unclear, possible anaphylaxis Those living in a remote area away from medical care/access

13. Self- injectable Epinephrine Everyone who has an Epinephrine syringe needs: Written instructions on how and when to use Epinephrine To know what they should do if they have needed to use the device (i.e. to call an ambulance) To be aware of the expiry dates of the device and know now and where they obtain a replacement. To carry their treatment with them at all times. In the case of children: Parents, relatives, child- minders, nursery staff, playgroup staff and schoolteachers should know how to give epinephrine ( and understand any allergen avoidance measures that should be taken) Canteen staff should be aware of the foods that these allergic children must avoid. Individuals should also be encouraged to wear an engraved identify bracelet or necklace giving details of their allergy and its treatment (www.medicalert.org.uk). This information can be life- saving. Individuals should also be encouraged to wear an engraved identify bracelet or necklace giving details of their allergy and its treatment (www.medicalert.org.uk). This information can be life- saving.

14. Audit objective To find out how many self- injectable epinephrine were prescribed in Paediatric Department in YDH during the period of one year ( June 2006- September 2007) To find criteria of anaphylaxis. To find and evaluate recognised standards/guidelines for prescribing self- injectable epinephrine. To find out whether prescription of self- injectable epinephrine in Paediatric Department in YDH was justified according to recognised standards. To find out whether the management of the patients who needed self- injectable epinephrine was appropriate and whether it was based on current knowledge and recognised standards. To discuss how to improve management of the patients who require self- injectable epinephrine. To decide whether and what guidelines regarding prescription of self- injectable epinephrine should be implemented in Paediatric Department in YDH.

15. Audit methodology Retrospective Study Sample Size- 25 children who have been prescribed self- injectable epinephrine in Paediatric Department in YDH during the period of one year ( June 2006- September 2007) Professional literature search Evaluation of 18 articles from literature regarding anaphylaxis and prescription of self- injectable epinephrine. Majority of articles are no more than 5 years old. Majority of articles contain information regarding indications for prescribing self- injectable epinephrine. Minority of articles say clearly which patients should be prescribed self- injectable epinephrine.

16. Audit results

17. Patients with anaphylaxis (n- 16)

19. Patients with increased risk of anaphylaxis ( n-5 ) 1. general rash - peanuts ( oral chlorphenamine). 2. swelling and irritation of back of throat –peanuts 3. local urticaria - cream containing peanuts and perioral rash - fish and perioral rash - fish 4. urticaria and periorbital angioedema - eggs and peanuts ( no treatment required). ( no treatment required). 5. perioral rash and swelling – peanuts In all above cases causative allergen was identified by skin prick tests or RAST.

20. Unjustified prescription (n-4) 1. rash to eggs (confirmed by tests, no treatment required). 2. rash, facial and eyes swelling to pollens? (not confirmed by tests, needed oral chlorphenamine). 3. facial, periorbital swelling and throat tightness to tuna, haddock, mayonnaise? ( not confirmed in tests, oral chlorphenamine). 4. urticaria, lips and ears swelling and vomiting 2x,normal BP and normal HR, no bronchospasm – no obvious trigger (not tested, IM adrenaline, oral prednisolone, oral chlorphenamine).

21. Audit conclusions There are not any recognized standards or guidelines for prescribing self-injectable epinephrine in the UK at the moment. Professional literature search and evaluation of articles have showed that self-injectable epinephrine should be prescribed for children who have experienced anaphylaxis and considered for persons who have not experienced anaphylaxis but are at increased risk of anaphylaxis.

22. Audit conclusions Prescription of self-injectable epinephrine in Peadiatric Department in YDH is not based on any local guidelines. In majority of the cases prescription of epinephrine was justified. 11/16 patients with anaphylaxis underwent tests to confirm the causative allergen. 7/16 patients with anaphylaxis were admitted to Ward 10. It was not clearly stated in the notes whether the patients were explained when and how to use self- injectable epinephrine. It was not written in the notes whether the patients were encouraged to buy and carry identify bracelets. There was nothing written in the notes about liaison with schools, nurseries, child-minders.

23. Audit recommendations To introduce guidelines regarding indications for prescription of self-injectable epinephrine in Paediatric Department in YDH. To introduce guidelines instructing how each patient who needs to have self-injectable epinephrine prescribed should be managed. To follow guidelines every time when self- injectable epinephrine is considered or needs to be prescribed. To do re-audit in 2 years in order to check compliance of the guidelines.